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5-HT4 Receptors in Lower Urinary Tract Tissues

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5-HT4 Receptors in the Brain and Periphery

Part of the book series: Biotechnology Intelligence Unit ((BIOIU))

Abstract

Interest in the role of 5-HT in the physiology and pathophysiology of the lower urinary tract (LUT), and its effect on neurotransmission in the bladder and urethra, has developed considerably over the last 20 years,1,2 reflecting the increased awareness of therapeutic potential and the relative inadequacy of current therapies for LUT disorders. 5-HT is recognized now as an ubiquitous intercellular signaling molecule. A great diversity of cell types can synthesize, store, release, uptake, as well as respond to extracellular 5-HT. This, coupled with the tremendous number and diversity of receptor proteins, implicates 5-HT in many physiological and pathophysiological processes. The importance of 5-HT in the regulation of the behavior of the “hollow organs” (e.g., discrete parts of the alimentary tract, the heart, the vasculature, and the bladder) has been well established.3–5 It is now clear that the many receptors for 5-HT (at least 14 known subtypes) allow for so many forms of modulation that tremendous subtleties in organ function can be introduced by selective receptor subtype activation or antagonism. Largely because 5-HT functions as a modulatory, rather than direct, transmitter in so many organs, the attractiveness of selective interaction with 5-HT receptors is great. Clearly, the opportunities for new, selective disease therapies are tremendous, and diseases of the LUT, which are poorly served by current drugs, are a key area for advancement in an ever-aging population.

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References

  1. Delaere KP, Debruyne FM, Booij LH. Influence of ketanserin (serotonin antagonist) on bladder and urethral function. Urology 1987; 29 (6): 669–73.

    Article  PubMed  CAS  Google Scholar 

  2. Andersson KE. Pharmacology of lower urinary tract smooth muscles and penile erectile tissues. Pharmacol Rev 1993; 45: 253308.

    Google Scholar 

  3. Ormsbee HS, Fondacaro JD. Minireview: Action of serotonin in the gastrointestinal tract. Proc Soc Exp Biol Med 1985; 178: 333–338.

    PubMed  CAS  Google Scholar 

  4. Ford APDW, Clarke DE. The 5-HT4 receptor. Med Res Rev 1993; 13 (6): 633–662.

    Article  PubMed  CAS  Google Scholar 

  5. Villalon CM, de Vries P, Saxena PR. Serotonin receptors as cardiovascular targets. Drug Discovery Today, 1997; 2 (7): 294–300.

    Article  CAS  Google Scholar 

  6. Gerald C, Adham N, Kao et al. The 5-HT4 receptor: molecular cloning and pharmacological characterization of two splice variants. EMBO J 1995; 14: 2206.

    Google Scholar 

  7. Cohen ML. Canine, but not rat bladder contracts to serotonin via activation of 5HT2 receptors. J Urology 1990; 143 (5): 1037–40.

    CAS  Google Scholar 

  8. Callahan SM, Creed KE. Electrical and mechanical activity of the isolated lower urinary tract of the guinea-pig. Br J Pharmacol 1981; 74: 353–358.

    Article  PubMed  CAS  Google Scholar 

  9. Saxena PR, Heiligers J, Mylecharane EJ et al. Excitatory 5- hydroxytryptamine receptors in the cat urinary bladder are of the M- and 5-HT2-type. J Auton Pharmacol 1985; 5: 101–107.

    Article  PubMed  CAS  Google Scholar 

  10. Holt SE, Cooper M, Wyllie JH. On the nature of the receptor mediating the action of 5-hydroxytryptamine in potentiating responses of the mouse urinary bladder strip to electrical stimulation. NaunynSchmiedeberg’s Arch Pharmacol 1986; 334 (4): 333–40.

    Article  PubMed  CAS  Google Scholar 

  11. Cleal A, Corsi M, Feniuk W et al. Potentiating action of 5-hydroxytryptamine (5-HT) on electrically-induced contractions in the mouse urinary bladder. Br J Pharmacol 1989; 97: 564 P.

    Google Scholar 

  12. Hills J, Meldrum LA, Klarskov P et al. A novel non-adrenergic, noncholinergic nerve-mediated relaxation of the pig bladder neck: an examination of possible neurotransmitter candidates. Eur J Pharmacol 1984; 99: 287–293.

    Article  PubMed  CAS  Google Scholar 

  13. Bowers CW, Kolton L. The efferent role of sensory axons in nerve-evoked contractions of bullfrog bladder. Neurosci 1987; 23: 1157–1168.

    Article  CAS  Google Scholar 

  14. Waikar MV, Ford APDW, Clarke DE. Evidence for an inhibitory 5HT4 receptor in urinary bladder of Rhesus and Cynomolgus monkeys. Br J Pharmacol 1994; 111 (1): 213–218.

    Article  PubMed  CAS  Google Scholar 

  15. Klarskov P, Horby-Petersen J. Influence of serotonin on lower urinary tract smooth muscle in vitro. Br j Urol 1986; 58: 507–513.

    Article  PubMed  CAS  Google Scholar 

  16. Hindmarsh JR, Idowu OA, Yeates WK et al. Pharmacology of electrically evoked contractions of human bladder. Br J Pharmacol 1977; 61: n5 P.

    Article  Google Scholar 

  17. Corsi M, Pietra C, Toson G et al. Pharmacological analysis of 5hydroxytryptamine effects on electrically stimulated human isolated urinary bladder. Br J Pharmacol 1991; 104 (3): 719–25.

    Article  PubMed  CAS  Google Scholar 

  18. Bockaert J, Fozard JR, Dumuis A et al. The 5-HT4 receptor: a place in the sun. Trends in Pharmacol Sci 1992; 13: 141–145.

    Article  CAS  Google Scholar 

  19. Tonini M, Messori E, Franceschetti GP et al. Characterization of the 5-HT receptor potentiating neuromuscular cholinergic transmission in strips of human isolated detrusor muscle. Br J Pharmacol 1994; 113 (1): 1–2.

    Article  PubMed  CAS  Google Scholar 

  20. Gale JD, Grossman CJ, Whitehead JWF et al. GR 113808: a novel selective antagonist with high affinity at the 5-HT4 receptor. Br J Pharmacol 1994; 111, 332–338.

    Article  PubMed  CAS  Google Scholar 

  21. Candura SM, Messori E, Franceschetti GP et al. Neural 5-HT4 receptors in the human isolated detrusor muscle: effects of indole, benzimidazolone and substituted benzamide agonists and antagonists. Br j Pharmacol 1996; 118 (8): 1965–70.

    Article  PubMed  CAS  Google Scholar 

  22. Gale JD, Reeves JJ, Bunce KT. Antagonism of the gastroprokinetic effect of metoclopramide by GR 125487, a potent and selective 5-HT4 receptor antagonist. J Gastrointest Motil 1993; 5: 192.

    Google Scholar 

  23. Schiavone A, Giraldo E, Giudici L et al. DAU 6285: a novel antagonist at the putative 5-HT4 receptors. Life Sci 1992; 51: 583–592.

    Article  PubMed  CAS  Google Scholar 

  24. Eglen RM, Bley K, Bonhaus DW et al. RS-23597–190: a potent and selective 5-HT4 receptor antagonist Br J Pharmacol 1993; 115: 1387–1389.

    Article  Google Scholar 

  25. Messori E, Rizzi CA, Candura SM et al. 5-Hydroxytryptamine receptors that facilitate excitatory neuromuscular transmission in the guinea-pig isolated detrusor muscle. Br J Pharmacol 1995; 115 (4): 677–683.

    Article  PubMed  CAS  Google Scholar 

  26. McCallum RW, Prakash C, Campoli-Richards D et al. Cisapride: A preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use as a prokinetic agent in gastrointestinal motility disorders. Drugs 1988; 36: 652–681.

    Article  PubMed  CAS  Google Scholar 

  27. McCallum RW. Cisapride: a new class of prokinetic agent. Am J Gastroenterol 1991; 86: 135–149.

    PubMed  CAS  Google Scholar 

  28. Nestler JE, Stratton MA, Hakim CA. Effect of metoclopramide on diabetic neurogenic bladder. Clin Pharm 1983; 2: 83–85.

    PubMed  CAS  Google Scholar 

  29. Kumar BB. Urinary incontinence associated with metoclopramide. JAMA 1984; 251 (12): 1553.

    Article  PubMed  CAS  Google Scholar 

  30. Binnie NR, Creasey GH, Edmond P et al. The action of cisapride on the chronic constipation of paraplegia. Paraplegia 1988; 26: 151–158.

    Article  PubMed  CAS  Google Scholar 

  31. Boyd IW, Rohan AP. Urinary disorders associated with cisapride. Med J Aus 1994; 160: 579–580.

    CAS  Google Scholar 

  32. Pillar’s PI, Wood SM. Cisapride increases micturition frequency. J Clin Gastroenterol 1994; 19(4)336–346.

    Article  Google Scholar 

  33. Franceschetti GP, Candura SM, Vicini D et al. Cisapride enhances detrusor contractility and improves micturition in a woman with lazy bladder. Scand J Urol Nephrol 1997; 31 (2): 209–210.

    Article  PubMed  CAS  Google Scholar 

  34. Tonini M, Candura SM. 5-HT4 Receptor agonists and bladder disorders. Trends Pharmacol Sci 1996; 17 (9): 314.

    PubMed  CAS  Google Scholar 

  35. Vaidyanathan S, Rao MS, Chary KS et al. Clinical import of serotonin activity in the bladder and urethra. J Urol 1981; 125 (1): 42–3.

    PubMed  CAS  Google Scholar 

  36. Physicians Desk Reference, 51st edition. Montvale, NJ: Product Information. Medical Economic Company, 1997; 935: 2828.

    Google Scholar 

  37. Sancho A, Martinez-Mir I, Palop V. Pollakiuria and micturition syndrome related to fluoxetine (letter). Medicina Clinica 1995; 105 (15): 598–599.

    PubMed  CAS  Google Scholar 

  38. Houston D, van Houtte P. Serotonin and the vascular system: role in health and disease and implications for therapy. Am J Hypertens 1988; 1: 317S - 328S.

    Google Scholar 

  39. Hollenberg N. Serotonin and the peripheral circulation. J Hypertens 1986; 4 (suppl 1): S23 - S27.

    CAS  Google Scholar 

  40. Nemoto N, Kawaoi A, Shikata T. Immunohistochemical demonstration of serotonin (5-HT) containing cells in the human and rat small intestine. Biomed Res 1982; 3: 181–187.

    CAS  Google Scholar 

  41. Petterson G, Ahlman H, Dahlstrom A et al. The effect of transmural field stimulation on the serotonin content in rat duodenal enterochromaffin cells-in vitro. Acta Physiol Scand 1979; 107: 83–87.

    Article  Google Scholar 

  42. Furness JB, Costa M. Neurones with 5-hydroxytryptamine-like immunoreactivity in the enteric nervous system: Their projections in the guinea-pig small intestine. Neuroscience 1982; 7: 341–349.

    Article  PubMed  CAS  Google Scholar 

  43. Fetissof F, Dubois MP, Arbeille-Brassart B et al. Endocrine cells in the prostate gland, urothelium and Brenner tumors. Immunohistological and ultrastructural studies. Virchow Arch B, Cell Pathology and Molecular Pathology 1983; 42 (1): 53–64.

    CAS  Google Scholar 

  44. Iwanaga T, Han H, Hoshi O et al.Topographical relation between serotonin-containing paraneurons and peptidergic neurons in the intestine and urethra. Biological Signals 1994; 3 (5): 259–70.

    Article  PubMed  CAS  Google Scholar 

  45. Iwanaga T, Hanyu S, Fujita T. Serotonin-immunoreactive cells of peculiar shape in the urethral epithelium of the human penis. Cell Tiss Res 1987; 249(1)51–6.

    Article  CAS  Google Scholar 

  46. Hanyu S, Iwanaga T, Kano K et al. Distribution of serotonin-immunoreactive paraneurons in the lower urinary tract of dogs. Am J Anatomy 1987; 180 (4): 349–56.

    Article  CAS  Google Scholar 

  47. Vittoria A, La Mura E, Cocca T et al. Serotonin-, somatostatin-and chromogranin A-containing cells of the urethro-prostatic complex in the sheep. An immunocytochemical and immunofluorescent study. J Anatomy 1990; 171: 169–78.

    CAS  Google Scholar 

  48. Christmas TJ, Rode J Characteristics of mast cells in normal bladder, bacterial cystitis and interstitial cystitis. Br J Urol 1991; 68 (5): 473–8.

    Article  PubMed  CAS  Google Scholar 

  49. Letourneau R, Sant GR, el-Mansoury M et al. Activation of bladder mast cells in interstitial cystitis. Int J Tissue React 1992; 14 (6): 307–12.

    PubMed  CAS  Google Scholar 

  50. Spanos C, Elmansoury M, Letournea R et al. Carbachol-induced bladder mast cell activation—augmentation by estradiol and implications for interstitial cystitis. Urology 1996; 48 (5): 809–816.

    Article  PubMed  CAS  Google Scholar 

  51. Moore KH, Nickson P, Richmond DH et al. Detrusor mast cells in refractory idiopathic instability. Br J Urol 1992; 70 (1): 17–21.

    Article  PubMed  CAS  Google Scholar 

  52. Frazer MI, Haylen B, Sissons M. Do women with idiopathic sensory urgency have early interstitial cystitis? Br J Urol 1990; 66 (3): 274–8.

    Article  PubMed  CAS  Google Scholar 

  53. Frishman WH, Huberfeld SH, Okin S et al. Serotonin and serotonin antagonism in cardiovascular and non-cardiovascular disease. J Clin Pharmacol 1995; 35: 541–572.

    PubMed  CAS  Google Scholar 

  54. Fozard JR. The 5-hydroxytryptamine-nitric oxide connection: the key link in the initiation of migraine? Arch Int Pharmacodyn 1995; 329: 111–119.

    PubMed  CAS  Google Scholar 

  55. Kaumann AJ. Do human atrial 5-HT4 receptors mediate arrhythmias? Trends Pharmacol Sci 1994; 15: 451–455.

    Article  PubMed  CAS  Google Scholar 

  56. Clark RD, Jahangir A, Flippin LA et al. RS-100235: A high affinity 5-HT4 receptor antagonist. Bioorg Med Chem Lett 1995; 5: 2119–2122.

    Article  CAS  Google Scholar 

  57. Hen R. Structural and functional conservation of serotonin receptors throughout evolution. In: Pichon Y, ed. Comparative Molecular Neurobiology. Basel: Birkhäuser Verlag, 1993: 266–278.

    Chapter  Google Scholar 

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© 1998 Springer-Verlag Berlin Heidelberg

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Ford, A.P.D.W., Kava, M.S. (1998). 5-HT4 Receptors in Lower Urinary Tract Tissues. In: Eglen, R.M. (eds) 5-HT4 Receptors in the Brain and Periphery. Biotechnology Intelligence Unit. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-05553-3_8

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  • DOI: https://doi.org/10.1007/978-3-662-05553-3_8

  • Publisher Name: Springer, Berlin, Heidelberg

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