Skip to main content
SpringerLink
Log in

Generation and Regulation of Spontaneous Contractions in the Prostate

  • Chapter
  • First Online:
Smooth Muscle Spontaneous Activity

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1124))

Abstract

Spontaneous myogenic contractions have been shown to be significantly upregulated in prostate tissue collected from men with Benign Prostatic Hyperplasia (BPH), an extremely common disorder of the ageing male. Although originally thought likely to be involved in ‘housekeeping’ functions, mixing prostatic secretions to prevent stagnation, these spontaneous myogenic contractions provide a novel opportunity to understand and treat BPH. This treatment potential differs from previous models, which focused exclusively on attenuating nerve-mediated neurogenic contractions. Previous studies in the rodent prostate have provided an insight into the mechanisms underlying the regulation of myogenic contractions. ‘Prostatic Interstitial Cells’ (PICs) within the prostate appear to generate pacemaker potentials, which arise from the summation of number of spontaneous transient depolarisations triggered by the spontaneous release of Ca2+ from internal stores and the opening of Ca2+-activated Cl− channels. Pacemaker potentials then conduct into neighbouring smooth muscle cells to generate spontaneous slow waves. These slow waves trigger the firing of ‘spike-like’ action potentials, Ca2+ entry and contraction, which are not attenuated by blockers of neurotransmission. However, these spontaneous prostatic contractions can be modulated by the autonomic nervous system. Here, we discuss the mechanisms underlying rodent and human prostate myogenic contractions and the actions of existing and novel pharmacotherapies for the treatment of BPH. Understanding the generation of human prostatic smooth muscle tone will confirm the mechanism of action of existing drugs, inform the identification and effectiveness of new pharmacotherapies, as well as predict patient outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA. Campbell-Walsh urology. 10th ed. Philadelphia: Saunders; 2011.

    Google Scholar 

  2. Amelar RD, Hotchkiss RS. The split ejaculate: its use in the management of male infertility. Fertil Steril. 1965;16:46–60.

    Article  CAS  PubMed  Google Scholar 

  3. Tauber PF, Zaneveld LJ, Propping D, Schumacher GF. Components of human split ejaculates. I. Spermatozoa, fructose, immunoglobulins, albumin, lactoferrin, transferrin and other plasma proteins. J Reprod Fertil. 1975;43(2):249–67.

    Article  CAS  PubMed  Google Scholar 

  4. Tauber PF, Zaneveld LJ, Propping D, Schumacher GF. Components of human split ejaculates. II. Enzymes and proteinase inhibitors. J Reprod Fertil. 1976;46(1):165–71.

    Article  CAS  PubMed  Google Scholar 

  5. Kavanagh JP. Isocitric and citric acid in human prostatic and seminal fluid: implications for prostatic metabolism and secretion. Prostate. 1994;24(3):139–42.

    Article  CAS  PubMed  Google Scholar 

  6. van der Graaf M, Schipper RG, Oosterhof GO, Schalken JA, Verhofstad AA, Heerschap A. Proton MR spectroscopy of prostatic tissue focused on the detection of spermine, a possible biomarker of malignant behavior in prostate cancer. MAGMA. 2000;10(3):153–9.

    PubMed  Google Scholar 

  7. Bedwal RS, Bahuguna A. Zinc, copper and selenium in reproduction. Experientia. 1994;50(7):626–40.

    Article  CAS  PubMed  Google Scholar 

  8. Ablin RJ, Soanes WA, Bronson P, Witebsky E. Precipitating antigens of the normal human prostate. J Reprod Fertil. 1970;22(3):573–4.

    Article  CAS  PubMed  Google Scholar 

  9. Rittenhouse HG, Finlay JA, Mikolajczyk SD, Partin AW. Human Kallikrein 2 (hK2) and prostate-specific antigen (PSA): two closely related, but distinct, kallikreins in the prostate. Crit Rev Clin Lab Sci. 1998;35(4):275–368.

    Article  CAS  PubMed  Google Scholar 

  10. Nelson PS, Gan L, Ferguson C, Moss P, Gelinas R, Hood L, et al. Molecular cloning and characterization of prostase, an androgen-regulated serine protease with prostate-restricted expression. Proc Natl Acad Sci U S A. 1999;96(6):3114–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chu TM, Wang MC, Kuciel R, Valenzuela L, Murphy GP. Enzyme markers in human prostatic carcinoma. Cancer Treat Rep. 1977;61(2):193–200.

    CAS  PubMed  Google Scholar 

  12. Dube JY, Frenette G, Paquin R, Chapdelaine P, Tremblay J, Tremblay RR, et al. Isolation from human seminal plasma of an abundant 16-kDa protein originating from the prostate, its identification with a 94-residue peptide originally described as beta-inhibin. J Androl. 1987;8(3):182–9.

    Article  CAS  PubMed  Google Scholar 

  13. Lin MF, Clinton GM. Human prostatic acid phosphatase has phosphotyrosyl protein phosphatase activity. Biochem J. 1986;235(2):351–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Niemi M, Harkonen M, Larmi TK. Enzymic histochemistry of human prostate. Localization of oxidative enzymes, esterase, and aminopeptidase in the normal and hyperplastic human prostate. Arch Pathol. 1963;75:528–37.

    CAS  PubMed  Google Scholar 

  15. Denis LJ, Prout GR Jr. Lactic dehydrogenase in prostatic cancer. Investig Urol. 1963;1:101–11.

    CAS  Google Scholar 

  16. Grayhack JT, Wendel EF, Oliver L, Lee C. Analysis of specific proteins in prostatic fluid for detecting prostatic malignancy. J Urol. 1979;121(3):295–9.

    Article  CAS  PubMed  Google Scholar 

  17. McNeal JE. Regional morphology and pathology of the prostate. Am J Clin Pathol. 1968;49(3):347–57.

    Article  CAS  PubMed  Google Scholar 

  18. McNeal JE. The prostate and prostatic urethra: a morphologic synthesis. J Urol. 1972;107(6):1008–16.

    Article  CAS  PubMed  Google Scholar 

  19. McNeal JE. Origin and evolution of benign prostatic enlargement. Investig Urol. 1978;15(4):340–5.

    CAS  Google Scholar 

  20. McNeal JE. The zonal anatomy of the prostate. Prostate. 1981;2(1):35–49.

    Article  CAS  PubMed  Google Scholar 

  21. McNeal JE. Normal histology of the prostate. Am J Surg Pathol. 1988;12(8):619–33.

    Article  CAS  PubMed  Google Scholar 

  22. Ayala AG, Ro JY, Babaian R, Troncoso P, Grignon DJ. The prostatic capsule: does it exist? Its importance in the staging and treatment of prostatic carcinoma. Am J Surg Pathol. 1989;13(1):21–7.

    Article  CAS  PubMed  Google Scholar 

  23. Oliveira DS, Dzinic S, Bonfil AI, Saliganan AD, Sheng S, Bonfil RD. The mouse prostate: a basic anatomical and histological guideline. Bosn J Basic Med Sci. 2016;16(1):8–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Neuhaus D, Mondry S. Comparative anatomy of the male guinea-pig and human lower urinary tract: histomorphology and three-dimensional reconstruction. Anat Histol Embryol. 2001;30(3):185–92.

    Article  PubMed  Google Scholar 

  25. Wang Y, Hayward S, Cao M, Thayer K, Cunha G. Cell differentiation lineage in the prostate. Differentiation. 2001;68(4–5):270–9.

    Article  CAS  PubMed  Google Scholar 

  26. Cunha GR, Hayward SW, Wang YZ, Ricke WA. Role of the stromal microenvironment in carcinogenesis of the prostate. Int J Cancer. 2003;107(1):1–10.

    Article  CAS  PubMed  Google Scholar 

  27. Toivanen R, Shen MM. Prostate organogenesis: tissue induction, hormonal regulation and cell type specification. Development. 2017;144(8):1382–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Gkonos PJ, Krongrad A, Roos BA. Neuroendocrine peptides in the prostate. Urol Res. 1995;23(2):81–7.

    Article  CAS  PubMed  Google Scholar 

  29. Shafik A, Shafik I, el-Sibai O. Identification of c-kit-positive cells in the human prostate: the interstitial cells of Cajal. Arch Androl. 2005;51(5):345–51.

    Article  CAS  PubMed  Google Scholar 

  30. Huizinga JD, Liu LW, Blennerhassett MG, Thuneberg L, Molleman A. Intercellular communication in smooth muscle. Experientia. 1992;48(10):932–41.

    Article  CAS  PubMed  Google Scholar 

  31. El-Alfy M, Pelletier G, Hermo LS, Labrie F. Unique features of the basal cells of human prostate epithelium. Microsc Res Tech. 2000;51(5):436–46.

    Article  CAS  PubMed  Google Scholar 

  32. Kellokumpu-Lehtinen P, Santti R, Pelliniemi LJ. Correlation of early cytodifferentiation of the human fetal prostate and Leydig cells. Anat Rec. 1980;196(3):263–73.

    Article  CAS  PubMed  Google Scholar 

  33. Farnsworth WE, Brown JR. Testosterone metabolism in the prostate. Natl Cancer Inst Monogr. 1963;12:323–9.

    CAS  PubMed  Google Scholar 

  34. Shimazaki J, Kurihara H, Ito Y, Shida K. Metabolism of testosterone in prostate. 2. Separation of prostatic 17-beta-ol-dehydrogenase and 5-alpha-reductase. Gunma J Med Sci. 1965;14(4):326–33.

    CAS  PubMed  Google Scholar 

  35. Wilson JD. The critical role of androgens in prostate development. Endocrinol Metab Clin N Am. 2011;40(3):577–90.. ix

    Article  CAS  Google Scholar 

  36. Cunha GR, Donjacour AA, Cooke PS, Mee S, Bigsby RM, Higgins SJ, et al. The endocrinology and developmental biology of the prostate. Endocr Rev. 1987;8(3):338–62.

    Article  CAS  PubMed  Google Scholar 

  37. Prins GS, Putz O. Molecular signaling pathways that regulate prostate gland development. Differentiation. 2008;76(6):641–59.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Silver RI, Wiley EL, Thigpen AE, Guileyardo JM, McConnell JD, Russell DW. Cell type specific expression of steroid 5 alpha-reductase 2. J Urol. 1994;152(2 Pt 1):438–42.

    Article  CAS  PubMed  Google Scholar 

  39. Bartsch G, Muller HR, Oberholzer M, Rohr HP. Light microscopic stereological analysis of the normal human prostate and of benign prostatic hyperplasia. J Urol. 1979;122(4):487–91.

    Article  CAS  PubMed  Google Scholar 

  40. Roehrborn CG. Pathology of benign prostatic hyperplasia. Int J Impot Res. 2008;20(Suppl 3):S11–8.

    Article  PubMed  Google Scholar 

  41. Adorini L, Penna G, Fibbi B, Maggi M. Vitamin D receptor agonists target static, dynamic, and inflammatory components of benign prostatic hyperplasia. Ann N Y Acad Sci. 2010;1193:146–52.

    Article  CAS  PubMed  Google Scholar 

  42. McNeal J. Pathology of benign prostatic hyperplasia. Insight into etiology. Urol Clin North Am. 1990;17(3):477–86.

    CAS  PubMed  Google Scholar 

  43. Shapiro E, Hartanto V, Lepor H. Quantifying the smooth muscle content of the prostate using double-immunoenzymatic staining and color assisted image analysis. J Urol. 1992;147(4):1167–70.

    Article  CAS  PubMed  Google Scholar 

  44. Shapiro E, Hartanto V, Lepor H. The response to alpha blockade in benign prostatic hyperplasia is related to the percent area density of prostate smooth muscle. Prostate. 1992;21(4):297–307.

    Article  CAS  PubMed  Google Scholar 

  45. Berry SJ, Strandberg JD, Saunders WJ, Coffey DS. Development of canine benign prostatic hyperplasia with age. Prostate. 1986;9(4):363–73.

    Article  CAS  PubMed  Google Scholar 

  46. Ehrlich Y, Foster RS, Bihrle R, Cheng L, Tong Y, Koch MO. Division of prostatic anterior fibromuscular stroma reduces urethral resistance in an ex vivo human prostate model. Urology. 2010;76(2):511.e10–3.

    Article  Google Scholar 

  47. Barry MJ, Cockett AT, Holtgrewe HL, McConnell JD, Sihelnik SA, Winfield HN. Relationship of symptoms of prostatism to commonly used physiological and anatomical measures of the severity of benign prostatic hyperplasia. J Urol. 1993;150(2 Pt 1):351–8.

    Article  CAS  PubMed  Google Scholar 

  48. Cunha GR, Chung LW, Shannon JM, Taguchi O, Fujii H. Hormone-induced morphogenesis and growth: role of mesenchymal-epithelial interactions. Recent Prog Horm Res. 1983;39:559–98.

    CAS  PubMed  Google Scholar 

  49. Isaacs JT. Prostate stem cells and benign prostatic hyperplasia. Prostate. 2008;68(9):1025–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kramer G, Mitteregger D, Marberger M. Is benign prostatic hyperplasia (BPH) an immune inflammatory disease? Eur Urol. 2007;51(5):1202–16.

    Article  CAS  PubMed  Google Scholar 

  51. Kondo S, Tashima Y, Morita T. Quantitative analysis of adrenergic alpha-1 and alpha-2 receptors in human prostatic urethral tissue. Br J Urol. 1993;72(1):68–73.

    Article  CAS  PubMed  Google Scholar 

  52. Yamada S, Ashizawa N, Ushijima H, Nakayama K, Hayashi E, Honda K. Alpha-1 adrenoceptors in human prostate: characterization and alteration in benign prostatic hypertrophy. J Pharmacol Exp Ther. 1987;242(1):326–30.

    CAS  PubMed  Google Scholar 

  53. Nasu K, Moriyama N, Kawabe K, Tsujimoto G, Murai M, Tanaka T, et al. Quantification and distribution of alpha 1-adrenoceptor subtype mRNAs in human prostate: comparison of benign hypertrophied tissue and non-hypertrophied tissue. Br J Pharmacol. 1996;119(5):797–803.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Klotz T, Mathers MJ, Bloch W, Nayal W, Engelmann U. Nitric oxide based influence of nitrates on micturition in patients with benign prostatic hyperplasia. Int Urol Nephrol. 1999;31(3):335–41.

    Article  CAS  PubMed  Google Scholar 

  55. Chapple CR, Crowe R, Gilpin SA, Gosling J, Burnstock G. The innervation of the human prostate gland--the changes associated with benign enlargement. J Urol. 1991;146(6):1637–44.

    Article  CAS  PubMed  Google Scholar 

  56. Caine M, Raz S, Zeigler M. Adrenergic and cholinergic receptors in the human prostate, prostatic capsule and bladder neck. Br J Urol. 1975;47(2):193–202.

    Article  CAS  PubMed  Google Scholar 

  57. Vaalasti A, Hervonen A. Nerve endings in the human prostate. Am J Anat. 1980;157(1):41–7.

    Article  CAS  PubMed  Google Scholar 

  58. Higgins JR, Gosling JA. Studies on the structure and intrinsic innervation of the normal human prostate. Prostate Suppl. 1989;2:5–16.

    Article  CAS  PubMed  Google Scholar 

  59. Ichihara I, Kallio M, Pelliniemi LJ. Light and electron microscopy of the ducts and their subepithelial tissue in the rat ventral prostate. Cell Tissue Res. 1978;192(3):381–90.

    Article  CAS  PubMed  Google Scholar 

  60. Pennefather JN, Lau WA, Mitchelson F, Ventura S. The autonomic and sensory innervation of the smooth muscle of the prostate gland: a review of pharmacological and histological studies. J Auton Pharmacol. 2000;20(4):193–206.

    Article  CAS  PubMed  Google Scholar 

  61. Christ GJ, Andersson KE. Rho-kinase and effects of Rho-kinase inhibition on the lower urinary tract. Neurourol Urodyn. 2007;26(6 Suppl):948–54.

    Article  CAS  PubMed  Google Scholar 

  62. Chapple CR, Aubry ML, James S, Greengrass PM, Burnstock G, Turner-Warwick RT, et al. Characterisation of human prostatic adrenoceptors using pharmacology receptor binding and localisation. Br J Urol. 1989;63(5):487–96.

    Article  CAS  PubMed  Google Scholar 

  63. James S, Chapple CR, Phillips MI, Greengrass PM, Davey MJ, Turner-Warwick RT, et al. Autoradiographic analysis of alpha-adrenoceptors and muscarinic cholinergic receptors in the hyperplastic human prostate. J Urol. 1989;142(2 Pt 1):438–44.

    Article  CAS  PubMed  Google Scholar 

  64. Hieble JP, Caine M, Zalaznik E. In vitro characterization of the alpha-adrenoceptors in human prostate. Eur J Pharmacol. 1985;107(2):111–7.

    Article  CAS  PubMed  Google Scholar 

  65. Hedlund H, Andersson KE, Larsson B. Alpha-adrenoceptors and muscarinic receptors in the isolated human prostate. J Urol. 1985;134(6):1291–8.

    Article  CAS  PubMed  Google Scholar 

  66. Tsujii T, Azuma H, Yamaguchi T, Oshima H. A possible role of decreased relaxation mediated by beta-adrenoceptors in bladder outlet obstruction by benign prostatic hyperplasia. Br J Pharmacol. 1992;107(3):803–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Drescher P, Eckert RE, Madsen PO. Smooth muscle contractility in prostatic hyperplasia: role of cyclic adenosine monophosphate. Prostate. 1994;25(2):76–80.

    Article  CAS  PubMed  Google Scholar 

  68. Haynes JM. beta(2) and beta(3)-adrenoceptor inhibition of alpha(1)-adrenoceptor-stimulated Ca(2+) elevation in human cultured prostatic stromal cells. Eur J Pharmacol. 2007;570(1–3):18–26.

    Article  CAS  PubMed  Google Scholar 

  69. Goepel M, Wittmann A, Rubben H, Michel MC. Comparison of adrenoceptor subtype expression in porcine and human bladder and prostate. Urol Res. 1997;25(3):199–206.

    Article  CAS  PubMed  Google Scholar 

  70. Calmasini FB, Candido TZ, Alexandre EC, D’Ancona CA, Silva D, de Oliveira MA, et al. The beta-3 adrenoceptor agonist, mirabegron relaxes isolated prostate from human and rabbit: new therapeutic indication? Prostate. 2015;75(4):440–7.

    Article  CAS  PubMed  Google Scholar 

  71. Kyprianou N, Benning CM. Suppression of human prostate cancer cell growth by alpha1-adrenoceptor antagonists doxazosin and terazosin via induction of apoptosis. Cancer Res. 2000;60(16):4550–5.

    CAS  PubMed  Google Scholar 

  72. Garrison JB, Kyprianou N. Doxazosin induces apoptosis of benign and malignant prostate cells via a death receptor-mediated pathway. Cancer Res. 2006;66(1):464–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Liou SF, Lin HH, Liang JC, Chen IJ, Yeh JL. Inhibition of human prostate cancer cells proliferation by a selective alpha1-adrenoceptor antagonist labedipinedilol-A involves cell cycle arrest and apoptosis. Toxicology. 2009;256(1–2):13–24.

    Article  CAS  PubMed  Google Scholar 

  74. Hori Y, Ishii K, Kanda H, Iwamoto Y, Nishikawa K, Soga N, et al. Naftopidil, a selective {alpha}1-adrenoceptor antagonist, suppresses human prostate tumor growth by altering interactions between tumor cells and stroma. Cancer Prev Res (Phila). 2011;4(1):87–96.

    Article  CAS  Google Scholar 

  75. Kanagawa K, Sugimura K, Kuratsukuri K, Ikemoto S, Kishimoto T, Nakatani T. Norepinephrine activates P44 and P42 MAPK in human prostate stromal and smooth muscle cells but not in epithelial cells. Prostate. 2003;56(4):313–8.

    Article  CAS  PubMed  Google Scholar 

  76. Bauer RM, Strittmatter F, Gratzke C, Gottinger J, Schlenker B, Reich O, et al. Coupling of alpha1-adrenoceptors to ERK1/2 in the human prostate. Urol Int. 2011;86(4):427–33.

    Article  CAS  PubMed  Google Scholar 

  77. Strittmatter F, Walther S, Roosen A, Rutz B, Schlenker B, Limmer S, et al. Activation of protein kinase B/Akt by alpha1-adrenoceptors in the human prostate. Life Sci. 2012;90(11–12):446–53.

    Article  CAS  PubMed  Google Scholar 

  78. Strittmatter F, Gratzke C, Walther S, Gottinger J, Beckmann C, Roosen A, et al. Alpha1-adrenoceptor signaling in the human prostate involves regulation of p38 mitogen-activated protein kinase. Urology. 2011;78(4):969.e7–13.

    Article  Google Scholar 

  79. Roehrborn CG. Three months’ treatment with the alpha1-blocker alfuzosin does not affect total or transition zone volume of the prostate. Prostate Cancer Prostatic Dis. 2006;9(2):121–5.

    Article  CAS  PubMed  Google Scholar 

  80. Andersson KE, Gratzke C. Pharmacology of alpha1-adrenoceptor antagonists in the lower urinary tract and central nervous system. Nat Clin Pract Urol. 2007;4(7):368–78.

    Article  CAS  PubMed  Google Scholar 

  81. Burnstock G. Purinergic signalling in the reproductive system in health and disease. Purinergic Signal. 2014;10(1):157–87.

    Article  CAS  PubMed  Google Scholar 

  82. Janssens R, Communi D, Pirotton S, Samson M, Parmentier M, Boeynaems JM. Cloning and tissue distribution of the human P2Y1 receptor. Biochem Biophys Res Commun. 1996;221(3):588–93.

    Article  CAS  PubMed  Google Scholar 

  83. Preston A, Frydenberg M, Haynes JM. A1 and A2A adenosine receptor modulation of alpha 1-adrenoceptor-mediated contractility in human cultured prostatic stromal cells. Br J Pharmacol. 2004;141(2):302–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Lam M, Mitsui R, Hashitani H. Electrical properties of purinergic transmission in smooth muscle of the guinea-pig prostate. Auton Neurosci. 2016;194:8–16.

    Article  CAS  PubMed  Google Scholar 

  85. Dunzendorfer U, Jonas D, Weber W. The autonomic innervation of the human prostate. Histochemistry of acetylcholinesterase in the normal and pathologic states. Urol Res. 1976;4(1):29–31.

    Article  CAS  PubMed  Google Scholar 

  86. Hedlund P, Ekstrom P, Larsson B, Alm P, Andersson KE. Heme oxygenase and NO-synthase in the human prostate—relation to adrenergic, cholinergic and peptide-containing nerves. J Auton Nerv Syst. 1997;63(3):115–26.

    Article  CAS  PubMed  Google Scholar 

  87. Vaalasti A, Hervonen A. Autonomic innervation of the human prostate. Investig Urol. 1980;17(4):293–7.

    CAS  Google Scholar 

  88. Witte LP, Chapple CR, de la Rosette JJ, Michel MC. Cholinergic innervation and muscarinic receptors in the human prostate. Eur Urol. 2008;54(2):326–34.

    Article  CAS  PubMed  Google Scholar 

  89. Seki N, Suzuki H. Electrical and mechanical activity of rabbit prostate smooth muscles in response to nerve stimulation. J Physiol. 1989;419:651–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Lau WA, Ventura S, Pennefather JN. Pharmacology of neurotransmission to the smooth muscle of the rat and the guinea-pig prostate glands. J Auton Pharmacol. 1998;18(6):349–56.

    Article  CAS  PubMed  Google Scholar 

  91. Lau WA, Pennefather JN, Mitchelson FJ. Cholinergic facilitation of neurotransmission to the smooth muscle of the guinea-pig prostate gland. Br J Pharmacol. 2000;130(5):1013–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Fernandez JL, Rivera L, Lopez PG, Recio P, Vela-Navarrete R, Garcia-Sacristan A. Characterization of the muscarinic receptor mediating contraction of the dog prostate. J Auton Pharmacol. 1998;18(4):205–11.

    Article  CAS  PubMed  Google Scholar 

  93. White CW, Short JL, Haynes JM, Matsui M, Ventura S. Contractions of the mouse prostate elicited by acetylcholine are mediated by M(3) muscarinic receptors. J Pharmacol Exp Ther. 2011;339(3):870–7.

    Article  CAS  PubMed  Google Scholar 

  94. Bloch W, Klotz T, Loch C, Schmidt G, Engelmann U, Addicks K. Distribution of nitric oxide synthase implies a regulation of circulation, smooth muscle tone, and secretory function in the human prostate by nitric oxide. Prostate. 1997;33(1):1–8.

    Article  CAS  PubMed  Google Scholar 

  95. Burnett AL, Maguire MP, Chamness SL, Ricker DD, Takeda M, Lepor H, et al. Characterization and localization of nitric oxide synthase in the human prostate. Urology. 1995;45(3):435–9.

    Article  CAS  PubMed  Google Scholar 

  96. Gradini R, Realacci M, Ginepri A, Naso G, Santangelo C, Cela O, et al. Nitric oxide synthases in normal and benign hyperplastic human prostate: immunohistochemistry and molecular biology. J Pathol. 1999;189(2):224–9.

    Article  CAS  PubMed  Google Scholar 

  97. Takeda M, Tang R, Shapiro E, Burnett AL, Lepor H. Effects of nitric oxide on human and canine prostates. Urology. 1995;45(3):440–6.

    Article  CAS  PubMed  Google Scholar 

  98. Haynes JM, Cook AL. Protein kinase G-induced activation of K(ATP) channels reduces contractility of human prostate tissue. Prostate. 2006;66(4):377–85.

    Article  CAS  PubMed  Google Scholar 

  99. Denninger JW, Marletta MA. Guanylate cyclase and the.NO/cGMP signaling pathway. Biochim Biophys Acta. 1999;1411(2–3):334–50.

    Article  CAS  PubMed  Google Scholar 

  100. Collins SP, Uhler MD. Cyclic AMP- and cyclic GMP-dependent protein kinases differ in their regulation of cyclic AMP response element-dependent gene transcription. J Biol Chem. 1999;274(13):8391–404.

    Article  CAS  PubMed  Google Scholar 

  101. Watts SW, Cohen ML. Effect of bombesin, bradykinin, substance P and CGRP in prostate, bladder body and neck. Peptides. 1991;12(5):1057–62.

    Article  CAS  PubMed  Google Scholar 

  102. Palea S, Corsi M, Artibani W, Ostardo E, Pietra C. Pharmacological characterization of tachykinin NK2 receptors on isolated human urinary bladder, prostatic urethra and prostate. J Pharmacol Exp Ther. 1996;277(2):700–5.

    CAS  PubMed  Google Scholar 

  103. Langenstroer P, Tang R, Shapiro E, Divish B, Opgenorth T, Lepor H. Endothelin-1 in the human prostate: tissue levels, source of production and isometric tension studies. J Urol. 1993;150(2 Pt 1):495–9.

    Article  CAS  PubMed  Google Scholar 

  104. Kedia GT, Uckert S, Kedia M, Kuczyk MA. Effects of phosphodiesterase inhibitors on contraction induced by endothelin-1 of isolated human prostatic tissue. Urology. 2009;73(6):1397–401.

    Article  PubMed  Google Scholar 

  105. Gratzke C, Weinhold P, Reich O, Seitz M, Schlenker B, Stief CG, et al. Transient receptor potential A1 and cannabinoid receptor activity in human normal and hyperplastic prostate: relation to nerves and interstitial cells. Eur Urol. 2010;57(5):902–10.

    Article  CAS  PubMed  Google Scholar 

  106. Kitada S, Kumazawa J. Pharmacological characteristics of smooth muscle in benign prostatic hyperplasia and normal prostatic tissue. J Urol. 1987;138(1):158–60.

    Article  CAS  PubMed  Google Scholar 

  107. Strittmatter F, Gratzke C, Weinhold P, Steib CJ, Hartmann AC, Schlenker B, et al. Thromboxane A2 induces contraction of human prostate smooth muscle by Rho kinase- and calmodulin-dependent mechanisms. Eur J Pharmacol. 2011;650(2–3):650–5.

    Article  CAS  PubMed  Google Scholar 

  108. Walden PD, Lefkowitz GK, Ittmann M, Lepor H, Monaco ME. Mitogenic activation of human prostate-derived fibromuscular stromal cells by bradykinin. Br J Pharmacol. 1999;127(1):220–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Srinivasan D, Kosaka AH, Daniels DV, Ford AP, Bhattacharya A. Pharmacological and functional characterization of bradykinin B2 receptor in human prostate. Eur J Pharmacol. 2004;504(3):155–67.

    Article  CAS  PubMed  Google Scholar 

  110. Kester RR, Mooppan UM, Gousse AE, Alver JE, Gintautas J, Gulmi FA, et al. Pharmacological characterization of isolated human prostate. J Urol. 2003;170(3):1032–8.

    Article  CAS  PubMed  Google Scholar 

  111. Exintaris B, Klemm MF, Lang RJ. Spontaneous slow wave and contractile activity of the Guinea pig prostate. J Urol. 2002;168(1):315–22.

    Article  PubMed  Google Scholar 

  112. Van der Aa F, Roskams T, Blyweert W, De Ridder D. Interstitial cells in the human prostate: a new therapeutic target? Prostate. 2003;56(4):250–5.

    Article  PubMed  Google Scholar 

  113. Kusljic S, Exintaris B. The effect of estrogen supplementation on cell proliferation and expression of c-kit positive cells in the rat prostate. Prostate. 2010;70(14):1555–62.

    Article  CAS  PubMed  Google Scholar 

  114. Boesch ST, Dobler G, Ramoner R, Corvin S, Thurnher M, Bartsch G, et al. Effects of alpha1-adrenoceptor antagonists on cultured prostatic smooth muscle cells. Prostate Suppl. 2000;9:34–41.

    Article  CAS  PubMed  Google Scholar 

  115. Scarano WR, Cordeiro RS, Goes RM, Carvalho HF, Taboga SR. Tissue remodeling in Guinea pig lateral prostate at different ages after estradiol treatment. Cell Biol Int. 2005;29(9):778–84.

    Article  CAS  PubMed  Google Scholar 

  116. Cordeiro RS, Scarano WR, Goes RM, Taboga SR. Tissue alterations in the guinea pig lateral prostate following antiandrogen flutamide therapy. Biocell. 2004;28(1):21–30.

    CAS  PubMed  Google Scholar 

  117. Horsfall DJ, Mayne K, Ricciardelli C, Rao M, Skinner JM, Henderson DW, et al. Age-related changes in guinea pig prostatic stroma. Lab Investig. 1994;70(5):753–63.

    CAS  PubMed  Google Scholar 

  118. Shapiro E, Becich MJ, Hartanto V, Lepor H. The relative proportion of stromal and epithelial hyperplasia is related to the development of symptomatic benign prostate hyperplasia. J Urol. 1992;147(5):1293–7.

    Article  CAS  PubMed  Google Scholar 

  119. Crowcroft PJ, Szurszewski JH. A study of the inferior mesenteric and pelvic ganglia of Guinea-pigs with intracellular electrodes. J Physiol. 1971;219(2):421–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Yokota R, Burnstock G. Decentralisation of neurones in the pelvic ganglion of the guinea-pig: reinnervation by adrenergic nerves. Cell Tissue Res. 1983;232(2):399–411.

    Article  CAS  PubMed  Google Scholar 

  121. Ventura S, Lau WA, Buljubasich S, Pennefather JN. Calcitonin gene-related peptide (CGRP) inhibits contractions of the prostatic stroma of the rat but not the guinea-pig. Regul Pept. 2000;91(1–3):63–73.

    Article  CAS  PubMed  Google Scholar 

  122. Pennefather JN, Lau WA, Chin C, Story ME, Ventura S. alpha(1L)-adrenoceptors mediate noradrenaline-induced contractions of the guinea-pig prostate stroma. Eur J Pharmacol. 1999;384(1):25–30.

    Article  CAS  PubMed  Google Scholar 

  123. Najbar-Kaszkiel AT, Di Iulio JL, Li CG, Rand MJ. Characterisation of excitatory and inhibitory transmitter systems in prostate glands of rats, guinea pigs, rabbits and pigs. Eur J Pharmacol. 1997;337(2–3):251–8.

    Article  CAS  PubMed  Google Scholar 

  124. Lang RJ, Hashitani H. Role of prostatic interstitial cells in prostate motility. J Smooth Muscle Res. 2017;53(0):57–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Corradi LS, Jesus MM, Fochi RA, Vilamaior PS, Justulin LA Jr, Goes RM, et al. Structural and ultrastructural evidence for telocytes in prostate stroma. J Cell Mol Med. 2013;17(3):398–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Kusljic S, Dey A, Nguyen DTT, Lang RJ, Exintaris B. Prostatic interstitial cells in ageing guinea pig prostates. Curr Urol. 2007;1(3):141–4.

    Article  Google Scholar 

  127. Leong KG, Wang BE, Johnson L, Gao WQ. Generation of a prostate from a single adult stem cell. Nature. 2008;456(7223):804–8.

    Article  CAS  PubMed  Google Scholar 

  128. Lammie A, Drobnjak M, Gerald W, Saad A, Cote R, Cordon-Cardo C. Expression of c-kit and kit ligand proteins in normal human tissues. J Histochem Cytochem. 1994;42(11):1417–25.

    Article  CAS  PubMed  Google Scholar 

  129. Gevaert T, Lerut E, Joniau S, Franken J, Roskams T, De Ridder D. Characterization of subepithelial interstitial cells in normal and pathological human prostate. Histopathology. 2014;65(3):418–28.

    Article  PubMed  Google Scholar 

  130. Lang RJ, Nguyen DT, Matsuyama H, Takewaki T, Exintaris B. Characterization of spontaneous depolarizations in smooth muscle cells of the Guinea pig prostate. J Urol. 2006;175(1):370–80.

    Article  CAS  PubMed  Google Scholar 

  131. Shigemasa Y, Lam M, Mitsui R, Hashitani H. Voltage dependence of slow wave frequency in the guinea pig prostate. J Urol. 2014;192(4):1286–92.

    Article  PubMed  Google Scholar 

  132. Oh SJ, Kim KM, Chung YS, Hong EK, Shin SY, Kim SJ. Ion-channel currents of smooth muscle cells isolated from the prostate of guinea-pig. BJU Int. 2003;92(9):1022–30.

    Article  CAS  PubMed  Google Scholar 

  133. Lang RJ, Mulholland E, Exintaris B. Characterization of the ion channel currents in single myocytes of the guinea pig prostate. J Urol. 2004;172(3):1179–87.

    Article  CAS  PubMed  Google Scholar 

  134. Eckert RE, Schreier U, Drescher P, Madsen PO, Derouet H, Becht E, et al. Regulation of prostatic smooth muscle contractility by intracellular second messengers: implications for the conservative treatment of benign prostatic hyperplasia. Urol Int. 1995;54(1):6–21.

    Article  CAS  PubMed  Google Scholar 

  135. Sui GP, Wu C, Fry CH. Ca2+ currents in smooth muscle cells isolated from human prostate. Prostate. 2004;59(3):275–81.

    Article  CAS  PubMed  Google Scholar 

  136. Dey A, Nguyen DT, Lang RJ, Exintaris B. Spontaneous electrical waveforms in aging guinea pig prostates. J Urol. 2009;181(6):2797–805.

    Article  PubMed  Google Scholar 

  137. Exintaris B, Nguyen DT, Dey A, Lang RJ. Spontaneous electrical activity in the prostate gland. Auton Neurosci. 2006;126-127:371–9.

    Article  PubMed  Google Scholar 

  138. Lang RJ, Tonta MA, Takano H, Hashitani H. Voltage-operated Ca(2) (+) currents and Ca(2) (+) -activated Cl(−) currents in single interstitial cells of the guinea-pig prostate. BJU Int. 2014;114(3):436–46.

    CAS  PubMed  Google Scholar 

  139. Dey A, Kusljic S, Lang RJ, Exintaris B. Role of connexin 43 in the maintenance of spontaneous activity in the guinea pig prostate gland. Br J Pharmacol. 2010;161(8):1692–707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Lam M, Kerr KP, Exintaris B. Involvement of Rho-kinase signaling pathways in nerve evoked and spontaneous contractions of the Guinea pig prostate. J Urol. 2013;189(3):1147–54.

    Article  CAS  PubMed  Google Scholar 

  141. Lee SN, Chakrabarty B, Wittmer B, Papargiris M, Ryan A, Frydenberg M, et al. Age related differences in responsiveness to sildenafil and tamsulosin are due to myogenic smooth muscle tone in the human prostate. Sci Rep. 2017;7(1):10150.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  142. Powell MS, Li R, Dai H, Sayeeduddin M, Wheeler TM, Ayala GE. Neuroanatomy of the normal prostate. Prostate. 2005;65(1):52–7.

    Article  PubMed  Google Scholar 

  143. Nguyen DT, Dey A, Lang RJ, Ventura S, Exintaris B. Contractility and pacemaker cells in the prostate gland. J Urol. 2011;185(1):347–51.

    Article  PubMed  Google Scholar 

  144. Somlyo AP, Somlyo AV. Signal transduction and regulation in smooth muscle. Nature. 1994;372(6503):231–6.

    Article  CAS  PubMed  Google Scholar 

  145. Villa A, Podini P, Panzeri MC, Soling HD, Volpe P, Meldolesi J. The endoplasmic-sarcoplasmic reticulum of smooth muscle: immunocytochemistry of vas deferens fibers reveals specialized subcompartments differently equipped for the control of Ca2+ homeostasis. J Cell Biol. 1993;121(5):1041–51.

    Article  CAS  PubMed  Google Scholar 

  146. Herrmann-Frank A, Darling E, Meissner G. Functional characterization of the Ca(2+)-gated Ca2+ release channel of vascular smooth muscle sarcoplasmic reticulum. Pflugers Arch. 1991;418(4):353–9.

    Article  CAS  PubMed  Google Scholar 

  147. Exintaris B, Nguyen DT, Lam M, Lang RJ. Inositol trisphosphate-dependent Ca stores and mitochondria modulate slow wave activity arising from the smooth muscle cells of the Guinea pig prostate gland. Br J Pharmacol. 2009;156(7):1098–106.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  148. Lam M, Shigemasa Y, Exintaris B, Lang RJ, Hashitani H. Spontaneous Ca2+ signaling of interstitial cells in the guinea pig prostate. J Urol. 2011;186(6):2478–86.

    Article  CAS  PubMed  Google Scholar 

  149. Johnston L, Carson C, Lyons AD, Davidson RA, McCloskey KD. Cholinergic-induced Ca2+ signaling in interstitial cells of Cajal from the guinea pig bladder. Am J Physiol Ren Physiol. 2008;294(3):F645–55.

    Article  CAS  Google Scholar 

  150. Sergeant GP, Hollywood MA, McCloskey KD, McHale NG, Thornbury KD. Role of IP(3) in modulation of spontaneous activity in pacemaker cells of rabbit urethra. Am J Phys Cell Phys. 2001;280(5):C1349–56.

    Article  CAS  Google Scholar 

  151. Nguyen DT, Lang RJ, Exintaris B. alpha(1)-adrenoceptor modulation of spontaneous electrical waveforms in the guinea-pig prostate. Eur J Pharmacol. 2009;608(1–3):62–70.

    Article  CAS  PubMed  Google Scholar 

  152. Caputo A, Caci E, Ferrera L, Pedemonte N, Barsanti C, Sondo E, et al. TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. Science. 2008;322(5901):590–4.

    Article  CAS  PubMed  Google Scholar 

  153. Yang YD, Cho H, Koo JY, Tak MH, Cho Y, Shim WS, et al. TMEM16A confers receptor-activated calcium-dependent chloride conductance. Nature. 2008;455(7217):1210–5.

    Article  CAS  PubMed  Google Scholar 

  154. Zhu MH, Kim TW, Ro S, Yan W, Ward SM, Koh SD, et al. A Ca(2+)-activated Cl(−) conductance in interstitial cells of Cajal linked to slow wave currents and pacemaker activity. J Physiol. 2009;587(Pt 20):4905–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  155. Gomez-Pinilla PJ, Gibbons SJ, Bardsley MR, Lorincz A, Pozo MJ, Pasricha PJ, et al. Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract. Am J Physiol Gastrointest Liver Physiol. 2009;296(6):G1370–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  156. Hwang SJ, Blair PJ, Britton FC, O’Driscoll KE, Hennig G, Bayguinov YR, et al. Expression of anoctamin 1/TMEM16A by interstitial cells of Cajal is fundamental for slow wave activity in gastrointestinal muscles. J Physiol. 2009;587(Pt 20):4887–904.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  157. Liu W, Lu M, Liu B, Huang Y, Wang K. Inhibition of Ca(2+)-activated Cl(−) channel ANO1/TMEM16A expression suppresses tumor growth and invasiveness in human prostate carcinoma. Cancer Lett. 2012;326(1):41–51.

    Article  CAS  PubMed  Google Scholar 

  158. Oelke M, Bachmann A, Descazeaud A, Emberton M, Gravas S, Michel MC, et al. EAU guidelines on the treatment and follow-up of non-neurogenic male lower urinary tract symptoms including benign prostatic obstruction. Eur Urol. 2013;64(1):118–40.

    Article  PubMed  Google Scholar 

  159. McVary KT, Roehrborn CG, Avins AL, Barry MJ, Bruskewitz RC, Donnell RF, et al. Update on AUA guideline on the management of benign prostatic hyperplasia. J Urol. 2011;185(5):1793–803.

    Article  PubMed  Google Scholar 

  160. Rossi S, editor. Australian medicines handbook 2014. Adelaide: Australian Medicines Handbook Pty Ltd; 2014.

    Google Scholar 

  161. Roehrborn CG. Male lower urinary tract symptoms (LUTS) and benign prostatic hyperplasia (BPH). Med Clin North Am. 2011;95(1):87–100.

    Article  PubMed  Google Scholar 

  162. Raz S, Zeigler M, Caine M. Pharmacological receptors in the prostate. Br J Urol. 1973;45(6):663–7.

    Article  CAS  PubMed  Google Scholar 

  163. Chakrabarty B, Dey A, Lam M, Ventura S, Exintaris B. Tamsulosin modulates, but does not abolish the spontaneous activity in the guinea pig prostate gland. Neurourol Urodyn. 2015;34(5):482–8.

    Article  CAS  PubMed  Google Scholar 

  164. Lepor H, Gup DI, Baumann M, Shapiro E. Comparison of alpha 1 adrenoceptors in the prostate capsule of men with symptomatic and asymptomatic benign prostatic hyperplasia. Br J Urol. 1991;67(5):493–8.

    Article  CAS  PubMed  Google Scholar 

  165. Kojima Y, Sasaki S, Shinoura H, Hayashi Y, Tsujimoto G, Kohri K. Quantification of alpha1-adrenoceptor subtypes by real-time RT-PCR and correlation with age and prostate volume in benign prostatic hyperplasia patients. Prostate. 2006;66(7):761–7.

    Article  CAS  PubMed  Google Scholar 

  166. Oelke M, Giuliano F, Mirone V, Xu L, Cox D, Viktrup L. Monotherapy with tadalafil or tamsulosin similarly improved lower urinary tract symptoms suggestive of benign prostatic hyperplasia in an international, randomised, parallel, placebo-controlled clinical trial. Eur Urol. 2012;61(5):917–25.

    Article  CAS  PubMed  Google Scholar 

  167. Chang DF, Campbell JR. Intraoperative floppy iris syndrome associated with tamsulosin. J Cataract Refract Surg. 2005;31(4):664–73.

    Article  PubMed  Google Scholar 

  168. van Dijk MM, de la Rosette JJ, Michel MC. Effects of alpha(1)-adrenoceptor antagonists on male sexual function. Drugs. 2006;66(3):287–301.

    Article  PubMed  Google Scholar 

  169. Barendrecht MM, Koopmans RP, de la Rosette JJ, Michel MC. Treatment of lower urinary tract symptoms suggestive of benign prostatic hyperplasia: the cardiovascular system. BJU Int. 2005;95(Suppl 4):19–28.

    Article  CAS  PubMed  Google Scholar 

  170. McConnell JD, Roehrborn CG, Bautista OM, Andriole GL Jr, Dixon CM, Kusek JW, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med. 2003;349(25):2387–98.

    Article  CAS  PubMed  Google Scholar 

  171. Roehrborn CG, Siami P, Barkin J, Damiao R, Major-Walker K, Nandy I, et al. The effects of combination therapy with dutasteride and tamsulosin on clinical outcomes in men with symptomatic benign prostatic hyperplasia: 4-year results from the CombAT study. Eur Urol. 2010;57(1):123–31.

    Article  CAS  PubMed  Google Scholar 

  172. Gacci M, Corona G, Salvi M, Vignozzi L, McVary KT, Kaplan SA, et al. A systematic review and meta-analysis on the use of phosphodiesterase 5 inhibitors alone or in combination with alpha-blockers for lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol. 2012;61(5):994–1003.

    Article  CAS  PubMed  Google Scholar 

  173. Dey A, Lang RJ, Exintaris B. Nitric oxide signaling pathways involved in the inhibition of spontaneous activity in the guinea pig prostate. J Urol. 2012;187(6):2254–60.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Drug Discovery Biology, Monash Institute of Pharmaceutical Science, Melbourne, VIC, Australia

    Basu Chakrabarty, Sophie Lee & Betty Exintaris

Authors
  1. Basu Chakrabarty
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sophie Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Betty Exintaris
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Betty Exintaris .

Editor information

Editors and Affiliations

  1. Nagoya City University, Nagoya, Aichi, Japan

    Hikaru Hashitani

  2. Monash University, Melbourne, VIC, Australia

    Richard J. Lang

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chakrabarty, B., Lee, S., Exintaris, B. (2019). Generation and Regulation of Spontaneous Contractions in the Prostate. In: Hashitani, H., Lang, R. (eds) Smooth Muscle Spontaneous Activity. Advances in Experimental Medicine and Biology, vol 1124. Springer, Singapore. https://doi.org/10.1007/978-981-13-5895-1_8

Download citation

Publish with us

Policies and ethics

Search

Navigation