Pharmacology of Airway Smooth Muscle

  • I. W. Rodger
  • R. C. Small
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 98)


In undertaking to write on the subject of the pharmacology of airway smooth muscle we have deliberately chosen not to produce an exhaustive review of the literature on the subject. Given the space constraints, it would be inappropriate to try to do so. Instead we have chosen to focus upon the excitation-contraction (E/C) coupling and uncoupling mechanisms that exist in airway smooth muscle. Thus, this chapter presents both biochemical and pharmacological information on contraction and relaxation mechanisms. In the context of drug-induced relaxation of airway smooth muscle we have been selective in concentrating on the actions of those drugs (β-adrenoceptor agonists and alkylxanthines) that are currently the principal bronchodilators in the therapy of asthma. In presenting much of the information contained in this chapter we have attempted to cite key references. Where appropriate, reference to relevant review articles has also been made.


Airway Smooth Muscle Intracellular Store Airway Smooth Muscle Cell Muscarinic Agonist Tracheal Smooth Muscle 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Advenier C, Naline E, Renier A (1986) Effects of BAY k 8644 on contraction of the human isolated bronchus and guinea-pig trachea. Br J Pharmacol 88: 33–39PubMedGoogle Scholar
  2. Ahmed F, Foster RW, Small RC, Weston AH (1984) Some features of the spasmogenic actions of acetylcholine and histamine in guinea-pig isolated trachealis. Br J Pharmacol 83: 227–233PubMedGoogle Scholar
  3. Ahmed F, Foster RW, Small RC(1985) Some effects of nifedipine in guinea-pig isolated trachealis. Br J Pharmacol 84: 861–869Google Scholar
  4. Aksoy MO, Murphy RA, Kamm KE (1982) Role of Ca2+ and myosin light chain phosphorylation in regulation of smooth muscle. Am J Physiol 242: C109–C116PubMedGoogle Scholar
  5. Aksoy MO, Mras S, Kamm KE, Murphy RA (1983) Ca2+, cAMP and changes in myosin phosphorylation during contraction of smooth muscle. Am J Physiol 245: C255–C270PubMedGoogle Scholar
  6. Allen SL, Beech DJ, Foster RW, Morgan GP, Small RC (1985a) Electro-physiological and other aspects of the relaxant action of isoprenaline in guinea-pig isolated trachealis. Br J Pharmacol 86: 843–854PubMedGoogle Scholar
  7. Allen SL, Foster RW, Small RC, Towart R (1985b) The effects of the dihydropyridine BAY k 8644 in guinea-pig isolated trachea. Br J Pharmacol 86: 171–180PubMedGoogle Scholar
  8. Allen SL, Cortijo J, Foster RW, Morgan GP, Small RC, Weston AH (1986) Mechanical and electrical aspects of the relaxant action of aminophylline in guinea-pig isolated trachealis. Br J Pharmacol 88: 473–483PubMedGoogle Scholar
  9. Baba K, Kawanishi M, Satake T, Tomita T (1985) Effects of verapamil on the contractions of guinea-pig tracheal smooth muscle induced by Ca, Sr and Ba. Br J Pharmacol 84: 203–211PubMedGoogle Scholar
  10. Baron CB, Cunningham M, Strauss JF, Coburn RF (1984) Pharmacomechanical coupling in smooth muscle may involve phosphatidylinositol metabolism. Proc Natl Acad Sci USA 81: 6899–6903PubMedGoogle Scholar
  11. Baron CB, Pring M, Coburn RF (1989) Inositol lipid turnover and compartmentation in canine trachealis smooth muscle. Am J Physiol 256: C375–C383PubMedGoogle Scholar
  12. Barnes PJ, Cuss FM, Palmer JB (1986) The effect of airway epithelium on smooth muscle contractility in bovine trachea. Br J Pharmacol 86: 685–691Google Scholar
  13. Bergstrand H (1980) Phosphodiesterase inhibition and theophylline. Eur J Respir Dis [Suppl 109] 61: 37–44Google Scholar
  14. Berridge MJ, Irvine RF (1984) Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature 312: 315–321PubMedGoogle Scholar
  15. Berridge MJ, Irvine RF (1989) Inositol phosphates and cell signalling. Nature 341: 197–203PubMedGoogle Scholar
  16. Bewley JS, Chapman IE (1988) AH 21-132 a novel relaxant of airways smooth muscle. Br J Pharmacol 93: 52 PGoogle Scholar
  17. Bolton TB (1979) Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev 59: 606–718PubMedGoogle Scholar
  18. Bryson SE, Rodger IW (1987) Effects of phosphodiesterase inhibitors on normal and chemically-skinned isolated airways smooth muscle. Br J Pharmacol 92: 673–681PubMedGoogle Scholar
  19. Cameron AR, Kirkpatrick CT (1977) A study of excitatory neuromuscular transmission in bovine trachea. J Physiol (Lond) 270: 733–745Google Scholar
  20. Cameron AR, Johnson CF, Kirkpatrick CT, Kirkpatrick MCA (1983) The quest for the inhibitory neurotransmitter in bovine tracheal smooth muscle. Q J Exp Physiol 68: 413–426PubMedGoogle Scholar
  21. Chatterjee M, Tejada M (1986) Phorbol ester-induced contraction in chemically skinned vascular smooth muscle. Am J Physiol 251: C356–C361PubMedGoogle Scholar
  22. Chilvers ER, Challis J, Barnes PJ, Nahorski SR (1989) Mass changes of inositol(l,4,5)trisphosphate in trachealis muscle following agonist stimulation. Eur J Pharmacol 614: 587–590Google Scholar
  23. Coburn RF (1979) Electromechanical coupling in canine trachealis muscle: acetylcholine contractions. Am J Physiol 236: C177–C184PubMedGoogle Scholar
  24. Coburn RF, Yamaguchi T (1977) Membrane potential-dependent and –independent tension in canine trachealis. J Pharmacol Exp Ther 201: 276–284PubMedGoogle Scholar
  25. Cox JSG (1967) Disodium cromoglycate (FPL 670) (TntaF): a specific inhibitor of reaginic antibody-antigen mechanisms. Nature 216: 1328–1329PubMedGoogle Scholar
  26. Creese BR (1983) Calcium ions, drug action and airways obstruction. Pharmacol Ther 20: 357–375PubMedGoogle Scholar
  27. Dale MM, Obianime AW (1985) Phorbol myristate acetate causes in guinea pig lung parenchymal strip a maintained spasm resistant to isoprenaline. FEBS Lett 190: 6–10PubMedGoogle Scholar
  28. Dale MM, Obianime AW (1987) 4J3-PDBu contracts parenchymal strip and synergises with raised cytosolic calcium. Eur J Pharmacol 141: 23–32Google Scholar
  29. DeLanerolle P, Condit JR, Tanenbaum M, Adelstein RS (1982) Myosin phosphorylation, agonist concentration and contraction of tracheal smooth muscle. Nature 298: 871–872Google Scholar
  30. Duncan RA, Krzanowski JJ, Poison JB, Coffey RG, Szentivanyi A (1987) Polyphosphoinositide metabolism in canine tracheal smooth muscle (CTSM) in response to a cholinergic stimulus. Biochem Pharmacol 36: 307–310PubMedGoogle Scholar
  31. Farley JM, Miles PR (1977) Role of depolarisation in acetylcholine-induced contractions of dog trachealis muscle. J Pharmacol Exp Ther 201: 199–205PubMedGoogle Scholar
  32. Farmer SG, Fedan JS, Hay DWP, Raeburn D (1986) The effects of epithelium removal on the sensitivity of guinea-pig isolated trachealis to bronchodilator drugs. Br J Pharmacol 89: 407–414PubMedGoogle Scholar
  33. Fedan JS, Hay DWP, Farmer SG, Raeburn D (1988) Epithelial cells. Modulation of airway smooth muscle reactivity. In: Barnes PJ, Rodger IW, Thompson NC (eds) Asthma: basic mechanisms and clinical management. Academic, London, pp. 143–162Google Scholar
  34. Felbel J, Trockur B, Ecker T, Landgraf W, Hofmann F (1988) Regulation of cytosolic calcium by cAMP and cGMP in freshly isolated smooth muscle cells from bovine trachea. J Biol Chem 263: 16764–16771PubMedGoogle Scholar
  35. Foster RW, Small RC, Weston AH (1983a) The spasmogenic action of potassium chloride in guinea-pig trachealis. Br J Pharmacol 80: 553–559PubMedGoogle Scholar
  36. Foster RW, Small RC, Weston AH (1983b) Evidence that the spasmogenic action of tetraethylammonium in guinea-pig trachealis is both direct and dependent upon the cellular influx of calcium ions. Br J Pharmacol 79: 255–263PubMedGoogle Scholar
  37. Foster RW, Okpalugo BI, Small RC (1984) Antagonism of Ca2+ and other actions of verapamil in guinea-pig isolated trachealis. Br J Pharmacol 81: 499–507PubMedGoogle Scholar
  38. Fujiwara T, Suminoto K, Itoh T, Kuriyama H (1988) Relaxing actions of procaterol, a beta2-adrenoceptor stimulant, on smooth muscle cells of the dog trachea. Br J Pharmacol 93: 199–209PubMedGoogle Scholar
  39. Gerthoffer WT (1986) Calcium dependence of myosin phosphorylation and airway smooth muscle contraction and relaxation. Am J Physiol 250: C597–C604PubMedGoogle Scholar
  40. Gerthoffer WT, Murphy RA (1983) Myosin phosphorylation and regulation of cross-bridge cycle in tracheal smooth muscle. Am J Physiol 244: C182–C187PubMedGoogle Scholar
  41. Ghosh TK, Eis PS, Mullaney JM, Ebert CL, Gill DL (1988) Competitive, reversible, and potent antagonism of inositol 1,4,5-trisphosphate-activated calcium release by heparin. J Biol Chem 263: 11075–11079PubMedGoogle Scholar
  42. Ghosh TK, Mullaney JM, Tarazi FM, Gill DL (1989) GTP-activated communication between distinct inositol 1,4,5-trisphosphate-sensitive and -insensitive calcium pools. Nature 340: 236–239PubMedGoogle Scholar
  43. Giembycz MA, Rodger IW (1987) Electrophysiological and other aspects of excitation-contraction coupling and uncoupling in mammalian airways smooth muscle. Life Sci 41: 111–132PubMedGoogle Scholar
  44. Goldie RG, Papadimitriou JM, Paterson JW, Self H, Spina D (1986) Influence of the epithelium on responsiveness of guinea-pig isolated trachea to contractile and relaxant agonists, Br J Pharmacol 87: 5–14PubMedGoogle Scholar
  45. Grandordy BM, Barnes PJ (1986) Effects of antiasthma drugs on membrane phospholipid breakdwon in airway smooth muscle. Am Rev Respir Dis 133 (4): A179Google Scholar
  46. Grandordy BM, Barnes PJ (1987) Phosphoinositide turnover in airway smooth muscle. Am Rev Respir Dis 136: S17–S20.PubMedGoogle Scholar
  47. Grandordy BM, Cuss FM, Sampson AS, Palmer JB, Barnes PJ (1986) Phosphatidyli- nositol response to cholinergic agonists in airway smooth muscle: relationship to contraction and muscarinic receptor occupancy. J Pharmacol Exp Ther 238: 273–279PubMedGoogle Scholar
  48. Grandordy BM, Cuss FM, Barnes PJ (1987) Breakdown of phosphoinositides in airway smooth muscle: lack of influence of antiasthma drugs. Life Sci 41: 1621–1627PubMedGoogle Scholar
  49. Haeusler G, Richards JG, Thorens A (1981) Noradrenaline contractions in rabbit mesenteric arteries skinned with saponin. J Physiol (Lond) 321: 537–556Google Scholar
  50. Hai C-M, Murphy RA (1988) Cross-bridge phosphorylation and regulation of the latch state in smooth muscle. Am J Physiol 254: C99–C106PubMedGoogle Scholar
  51. Hai C-M, Murphy RA (1989) Ca2+, crossbridge phosphorylation and contraction. Annu Rev Physiol 51: 285–298PubMedGoogle Scholar
  52. Hall IP, Hill SJ (1988) (32-Adrenoceptor stimulation inhibits histamine-stimulated inositol phospholipid hydrolysis in bovine tracheal smooth muscle. Br J Pharmacol 95: 1204–1212Google Scholar
  53. Hall IP, Hill SJ (1989) Inhibition of histamine-stimulated inositol phospholipid hydrolysis by agents which increase cyclic AMP levels in bovine tracheal smooth muscle. Br J Pharmacol 97: 603–613PubMedGoogle Scholar
  54. Hall IP, Donaldson J, Hill SJ (1989) Inhibition of histamine-stimulated inositol phospholipid hydrolysis by agents which increase cyclic AMP levels in bovine tracheal smooth muscle. Br J Pharmacol 97: 603–613PubMedGoogle Scholar
  55. Hashimoto T, Hirata M, Ito Y (1985) A role for inositol 1,4,5-trisphosphate in the initiation of agonist-induced contractions of dog tracheal smooth muscle. Br J Pharmacol 86: 191–199PubMedGoogle Scholar
  56. Holroyde MC (1986) The influence of epithelium on responsiveness of guinea-pig isolated trachea. Br J Pharmacol 87: 501–507PubMedGoogle Scholar
  57. Honda K, Tomita T (1987) Electrical activity in isolated human tracheal muscle. Jpn J Physiol 37: 333–336PubMedGoogle Scholar
  58. Honda K, Satake T, Takagi K, Tomita T (1986) Effects of relaxants on electrical and mechanical activities in the guinea-pig tracheal muscle. Br J Pharmacol 87:P 665–671PubMedGoogle Scholar
  59. Irvine RF, Letcher AJ, Heslop JP, Berridge MJ (1986) The inositol tris/ tetrakisphosphate pathway - demonstration of Ins (l,4,5)P3-kinase activity in animal tissues. Nature 320: 631–633PubMedGoogle Scholar
  60. Ito Y, Itoh T (1984a) The roles of stored calcium in contraction of cat tracheal smooth muscle produced by electrical stimulation, acetylcholine and high K+. Br J Pharmacol 83: 677–676PubMedGoogle Scholar
  61. Ito Y, Itoh T (1984b) Effects of isoprenaline on the contraction-relaxation cycle in the cat trachea. Br J Pharmacol 83: 677–686PubMedGoogle Scholar
  62. Ito Y, Tajima K (1982) Dual effects of catecholamines on pre- and post-junctional membranes in the dog trachea. Br J Pharmacol 75: 433–440PubMedGoogle Scholar
  63. Jones CA, Madison JM, Tom-Moy M, Brown JK (1987) Muscarinic cholinergic inhibition of adenylate cyclase in airway smooth muscle. Am J Physiol 253: C97–C104PubMedGoogle Scholar
  64. Kamm KE, Stull JT (1985a) The function of myosin and myosin light chain kinase phosphorylation in smooth muscle. Annu Rev Pharmacol Toxicol 25: 593–620PubMedGoogle Scholar
  65. Kamm KE, Stull JT (1985b) Myosin phosphorylation, force and maximal shortening velocity in neurally-stimulated tracheal smooth muscle. Am J Physiol 249: C238–C247PubMedGoogle Scholar
  66. Kamm KE, Stull JT (1986) Activation of smooth muscle contraction: correlation between myosin phosphorylation and stiffness. Science 232: 80–82PubMedGoogle Scholar
  67. Kannan MS, Jager LP, Daniel EE, Garfield RE (1983) Effects of 4-aminopyridine and tetraethylammonium chloride on the electrical activity and cable properties of canine tracheal smooth muscle. J Pharmol Exp Ther 227: 706–715Google Scholar
  68. Karlsson JA, Persson CGA (1981) Influence of tracheal contraction on relaxant effects in vitro of theophylline and isoprenaline. Br J Pharmacol 74: 73–79PubMedGoogle Scholar
  69. Katsuki S, Murad F (1977) Regulation of adenosine cyclic 3,5-monophosphate and guanosine cyclic 3,5-monophosphate levels and contractility in bovine tracheal smooth muscle. Mol Pharmacol 13; 330–341PubMedGoogle Scholar
  70. Kirkpatrick CT (1981) Tracheobronchial smooth muscle. In: Bulbring E, Brading AF, Jones AW, Tomita T (eds) Smooth muscle: an assessment of current knowledge. Arnold, London, pp 385–395Google Scholar
  71. Kirkpatrick CT, Jenkinson HA, Cameron AR (1975) Interaction between drugs and potassium-rich solutions in producing contraction in bovine tracheal smooth muscle: Studies in normal and calcium-depleted tissues. Clin Exp Pharmacol Physiol 2: 559–570PubMedGoogle Scholar
  72. Kitazawa T, Kobayashi S, Horiuti K, Somlyo AV, Somlyo AP (1989) Receptor- coupled, permeabilised smooth muscle: role of the phosphatidylinositol cascade, G-proteins, and modulation of the contractile response to Ca2+. J Biol Chem 264: 5339–5342PubMedGoogle Scholar
  73. Kobayashi S, Somlyo AV, Somlyo AP (1988) Heparin inhibits the inositol 1,4,5-trisphosphate-dependent, but not the independent, calcium release induced by guanine nucleotide in vascular smooth muscle. Biochem Biophys Res Commun 153: 625–631PubMedGoogle Scholar
  74. Kolbeck RC, Speir WA, Carrier GO, Bransome ED (1979) Apparent irrelevance of cyclic nucleotides to the relaxation of tracheal smooth muscle induced by theophylline. Lung 156: 173–183PubMedGoogle Scholar
  75. Kotlikoff MI (1988) Calcium currents in isolated canine airway smooth muscle cells. Am J Physiol 254: C793–C801PubMedGoogle Scholar
  76. Kotlikoff MI, Murray RK, Reynolds EE (1987) Histamine-induced calcium release and phorbol antagonism in cultured airway smooth muscle cells. Am J Physiol 245: C561–C566Google Scholar
  77. Kroeger EA, Stephens NL (1975) Effect of tetraethylammonium on tonic airway smooth muscle: initiation of phasic electrical activity. Am J Physiol 228: 633–636PubMedGoogle Scholar
  78. Kumar MA (1978) The basis of beta-adrenergic bronchodilation. J Pharmacol Exp Ther 206: 528–534PubMedGoogle Scholar
  79. Kume H, Takai A, Tokuno H, Tomita T (1989) Regulation of Ca2+-dependent K+-channel activity in tracheal myocytes by phosphorylation. Nature 341: 152–154PubMedGoogle Scholar
  80. Langland JM, Rodger IW, Diamond J (1989) The effect of M and B 22948 on methacholine- and histamine-induced contraction and inositol 1,4,5-trisphosphate levels in guinea-pig tracheal tissue. Br J Pharmacol 98: 336–338Google Scholar
  81. Lohmann SM, Miech RP, Butcher FR (1977) Effects of isoproterenol, theophylline and carbachol on cyclic nucleotide levels and relaxation in bovine tracheal smooth muscle. Biochim Biophys Acta 499: 238–250PubMedGoogle Scholar
  82. Madison JM, Brown JK (1988) Differential inhibitory effects of forskolin, isoproterenol and dibutyryl cyclic adenosine monophosphate on phosphoinositide hydrolysis in canine tracheal smooth muscle. J Clin Invest 82: 1462–1465PubMedGoogle Scholar
  83. Marthan RJ, Savineau JP, Mironneau J (1985) Acetylcholine-induced contraction in human isolated bronchial smooth muscle: role of an intracellular calcium store. Respir Physiol 67: 127–135Google Scholar
  84. Marthan RJ, Armour CL, Johnson PR A, Black JL (1988) Extracellular calcium and human isolated airway muscle: ionophore A23187-induced contraction. Respir Physiol 71: 157–168PubMedGoogle Scholar
  85. Marthan RJ, Martin C, Amedee T, Mironneau J (1989) Calcium channel currents in isolated smooth muscle cells from human bronchus. J Appl Physiol 66: 1706–1714PubMedGoogle Scholar
  86. Martin C, Dacquet C, Mirroneau C, Mirroneau J (1989) Caffeine-induced inhibition of calcium channel current in cultured smooth muscle cells from pregnant rat myometrium. Br J Pharmacol 98: 493–498PubMedGoogle Scholar
  87. McCaig DJ, Rodger IW (1988) Electrophysiological effects of leukotriene D4 in guinea-pig airway smooth muscle. Br J Pharmacol 94: 729–736PubMedGoogle Scholar
  88. McCaig DJ, Souhrada JF (1980) Alteration of electrophysiological properties of airway smooth muscle from sensitized guinea-pigs. Respir Physiol 41: 49–60PubMedGoogle Scholar
  89. Meisheri KD, Ruegg JC, Paul RJ (1985) Studies on skinned fiber preparations. In: Grover AK, Daniel EE (eds) Calcium and contractility: smooth muscle. Humana, Clifton, pp 191–224Google Scholar
  90. Menkes H, Baraban JM, Snyder SH (1986) Protein kinase C regulates smooth muscle tension in guinea-pig trachea and ileum, Eur J Pharmacol 122; 19–28PubMedGoogle Scholar
  91. Merritt J, Armstrong WP, Hallam TJ, Jaxa-Chamiec A, Leigh BK, Moores KE, Rink TJ (1989) SK and F 96365, a novel inhibitor of receptor-mediated calcium entry and aggregation in Quin 2-loaded human platelets. Br J Pharmacol 98: 674 PGoogle Scholar
  92. Meurs H, Roffel AF, Postema JB, Timmermans A, Elzinga CRA, Kauffman HF, Zaagsma J (1988) Evidence for a direct relationship between phosphoinositide metabolism and airway smooth muscle contraction induced by muscarinic agonists. Eur J Pharmacol 156: 271–274PubMedGoogle Scholar
  93. Meurs H, Timmermans S, Van Amsterdam RGM, Brouwer F, Kauffman HF, Zaagsma J (1989) Muscarinic receptors in human airway smooth muscle are coupled to phosphoinositide metabolism. Eur J Pharmacol 164: 369–371PubMedGoogle Scholar
  94. Miller JR, Hawkins DJ, Wells JN (1986) Phorbol diesters alter contractile responses of porcine conronary artery. J Pharmacol Exp Ther 239: 38–42PubMedGoogle Scholar
  95. Miller-Hance WC, Miller JR, Wells, JN, Stull JT, Kamm KE (1988) Biochemical events associated with activation of smooth muscle contraction. J Biol Chem 263: 13979–13982PubMedGoogle Scholar
  96. Mong S, Hoffman K, Wu H-L, Crooke ST (1987) Leukotriene-induced hydrolysis of inositol lipids in guinea-pig lung. Mechanism of signal transduction for leukot- riene D4 receptors. Mol Pharmacol 31: 35–41PubMedGoogle Scholar
  97. Mong S, Miller J, Wu H-L, Crooke ST (1988) Leukotriene D4 receptor-mediated hydrolysis of phosphoinositide and mobilization of calcium in sheep tracheal smooth muscle cells. J Pharmacol Exp Ther 244: 508–515PubMedGoogle Scholar
  98. Mullaney JM, Yu M, Ghosh TK, Gill DL (1988) Calcium entry into the inositol 1,4,5-trisphosphate-releasable calcium pool is mediated by a GTP-regulatory mechanism. Proc Natl Acad Sci USA 85: 2499–2503PubMedGoogle Scholar
  99. Murlas CG, Doupnik CA (1989) Electromechanical coupling of ferret airway smooth muscle in response to leukotriene D4. J App Physiol 66: 1533–1538Google Scholar
  100. Murphy RA (1989) Contraction in smooth muscle cells. Annu Rev Physiol 51: 275–283PubMedGoogle Scholar
  101. Murray RK, Fluharty SJ, Kotlikoff MJ (1988) Phorbol ester blocks histamine-induced insoitol trisphosphate production in cultured airway smooth muscle. Am Rev Respir Dis 137: A309Google Scholar
  102. Nahorski SR, Batty I (1986) Inositol tetrakisphosphate: recent developments in PI metabolism and receptor function. Trends Pharmacol Sci 7: 83–85Google Scholar
  103. Newman DJ, Colella DF, Spainhour CB, Brann EG, Zabko-Potapovich B, Wardell JR (1978) cAMP-Phosphodiesterase inhibitors and tracheal smooth muscle relaxation. Biochem Pharmacol 27: 729–732Google Scholar
  104. Nishizuka Y (1983) Calcium, phospholipid turnover and transmembrane signalling. Philos Trans R Soc Lond [Biol] 302: 101–112Google Scholar
  105. Nishizuka Y (1988) The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature 334: 661–665PubMedGoogle Scholar
  106. Nouailhetas VLA, Lodge NJ, Twort CHC, Van Breemen C (1988) The intracellular calcium stores in rabbit trachealis. Eur J Pharmacol 157: 165–172PubMedGoogle Scholar
  107. Obianime AW, Hirst SJ, Dale MM (1988) Interactions between phorbol esters and agents which increase cytosolic calcium in guinea pig parenchymal strip: direct and indirect effects on the contractile response. J Pharmacol Exp Ther 247: 262–270PubMedGoogle Scholar
  108. Panettieri RA, Murray RK, DePalo LR, Yadvish PA, Kotlikoff MI (1989) A human airway smooth muscle cell line that retains physiological responsiveness. Am J Physiol 256: C329–C335Google Scholar
  109. Park S, Rasmussen H (1986a) Activation of tracheal smooth muscle contraction: synergism between Ca2+ and activators of protein kinase C. Proc Natl Acad Sci USA 82: 8835–8839Google Scholar
  110. Park S, Rasmussen H (1986b) Carbachol-induced protein phosphorylation changes in bovine tracheal smooth muscle. J Biol Chem 261: 15373–15379Google Scholar
  111. Parsons WJ, Ramkumar V, Stiles GL (1988) Isobutylmethylxanthine stimulates adenylate cyclase by blocking the inhibitory regulatory protein, Gi. Mol Pharmacol 34: 37–41PubMedGoogle Scholar
  112. Persechini A, Kamm KE, Stull JT (1986) Different phosphorylated forms of myosin in contracting tracheal smooth muscle. J Biol Chem 261: 6293–6299PubMedGoogle Scholar
  113. Persson CGA (1985) Experimental lung actions of xanthines In: Andersson KE, Persson CGA (eds) Anti-asthma xanthines and adenosine. Excerpta Medica, Amsterdam, pp 61–83Google Scholar
  114. Poison JB, Krzanowski JJ, Anderson WH, Fitzpatrick DF, Hwang DPC, Szentivanyi A (1979) Analysis of the relationship between pharmacological inhibition of cyclic nucleotide phosphodiesterase and relaxation of canine tracheal smooth muscle. Biochem Pharmacol 28: 1391–1395Google Scholar
  115. Poison JB, Krzanowski JJ, Szentivanyi A (1982) Inhibition of a high affinity cyclic AMP phosphodiesterase and relaxation of canine tracheal smooth muscle. Biochem Pharmacol 31: 3403–3406Google Scholar
  116. Putney JW (1986) A model for receptor-regulated calcium entry. Cell Calcium 7: 1–12PubMedGoogle Scholar
  117. Putney JW, Takemura H, Hughes AR, Horstman DA, Thastrup O (1989) How do inositol phosphates regulate calcium signalling? FASEB J 3: 1899–1905Google Scholar
  118. Raeburn D, Rodger IW (1984) Lack of effect of leukoriene D4 on Ca-uptake in airway smooth muscle. Br J Pharmacol 83: 499–504PubMedGoogle Scholar
  119. Raeburn D, Roberts JA, Rodger IW, Thomson NC (1986) Agonist-induced contractile responses of human bronchial muscle in vitro: effects of Ca2+ removal, La3+ and PY 108068. Eur J Pharmacol 121: 251–255PubMedGoogle Scholar
  120. Rasmussen H, Barrett PQ (1984) Calcium messenger system: an integrated view. Physiol Rev 64: 938–984PubMedGoogle Scholar
  121. Rasmussen H, Kojima I, Kojima K, Zawalich W, Appeldorf W (1984) Calcium as intracellular messenger: sensitivity modulation, C-kinase pathway and sustained cellular response, Adv Cyclic Nucleotide Res 18: 159–193Google Scholar
  122. Rasmussen H, Takuwa Y, Park S (1987) Protein kinase C in the regulation of smooth muscle contraction. FASEB J 1: 177–185Google Scholar
  123. Rodger IW (1986) Calcium ions and contraction of airways smooth muscle. In: Kay AB (ed) Asthma: clinical pharmacology and therapeutic progress. Blackwell, Oxford, pp 114–127Google Scholar
  124. Rodger IW (1987) Calcium channels in airway smooth muscle. Am Rev Respir Dis 136: S15–S17PubMedGoogle Scholar
  125. Rodger IW (1988) Biochemistry of airway smooth muscle contraction. In: Barnes PJ, Rodger IW, Thomson NC (eds) Asthma: basic mechanisms and clinical management. Academic, London, pp 57–79Google Scholar
  126. Ross CA, Meldolesi J, Milner TA, Satoh T, Supattapone S, Snyder SH (1989) Inositol 1,4,5-trisphosphate receptor localised to endoplasmic reticulum in cerebellar Pur kin je neurons. Nature 339: 468–470PubMedGoogle Scholar
  127. Saida K (1982) Intracellular Ca2+ release in skinned smooth muscle. J Gen Physiol 80: 191–192PubMedGoogle Scholar
  128. Saida K, Twort CHC, Van Breemen C (1988) The specific GTP requirement for inositol 1,4,5-trisphosphate-induced Ca2+ release from skinned vascular smooth muscle. J Cardiovasc Pharmacol 12: S47–S50PubMedGoogle Scholar
  129. Silver PJ, Stull JT (1982) Regulation of myosin light chain and phosphorylase phosphorylation in tracheal smooth muscle. J Biol Chem 257: 6145–6150PubMedGoogle Scholar
  130. Silver PJ, Stull JT (1984) Phosphorylation of myosin light chain and phosphorylase in tracheal smooth muscle in response to KC1 and carbachol. Mol Pharmacol 25: 267–274PubMedGoogle Scholar
  131. Small RC, Foster RW (1986) Airways smooth muscle: an overview of morphology, electrophysiology and aspects of the pharmacology of contraction and relaxation. In:Kay AB (ed) Asthma:clinical pharmacology and therapeutic progress. Blackwell, London, pp 101–113Google Scholar
  132. Small RC, Foster RW (1987) Electrophysiologic behaviour of normal and sensitized airway smooth muscle. Am Rev Respir Dis 136: S7–S11PubMedGoogle Scholar
  133. Small RC, Foster RW (1988) Electrophysiology of the airway smooth muscle cell. In:Barnes PJ, Rodger IW, Thompson NC (eds) Asthma: basic mechanisms and clinical management. Academic, London, pp 35–56Google Scholar
  134. Small RC, Boyle JP, Cortijo J, Curtis-Prior PB, Davies JM, Foster RW, Hofer P (1988a) The relaxant and spasmogenic effects of some xanthine derivatives acting on guinea-pig isolated trachealis muscle. Br J Pharmacol 94: 1091–1100PubMedGoogle Scholar
  135. Small RC, Foster RW, Boyle JP, Davies JM (1988b) The site and mechanism of the relaxant effects of aminophylline and other methylxanthines in isolated airways smooth muscle. In: Paton DM (ed) Adenosine and adenine nucleotides: physiology and pharmacology. Taylor and Francis, London, pp 271–280Google Scholar
  136. Small RC, Boyle JP, Duty S, Elliott KRF, Foster RW, Watt AJ (1989) Analysis of the relaxant effects of AH 21-132 in guinea-pig isolated trachealis. Br J Pharmacol 97: 1165–1173PubMedGoogle Scholar
  137. Sparrow MP, Pfitzer G, Gagelmann M, Ruegg JC (1984) Effect of calmodulin, Ca2+ and cAMP protein kinase on skinned tracheal smooth muscle. Am J Physiol 246: C308–C314PubMedGoogle Scholar
  138. Spat A, Bradford PG, McKinney JS, Rubin RP, Putney JW (1986) A saturable receptor for 32P-inositol-l,4,5-trisphosphate in hepatocytes and neutrophils. Nature 319: 514–516PubMedGoogle Scholar
  139. Spilker B, Minatoya H (1975) The role of bronchoconstrictors in evaluating smooth muscle relaxant activity. Arch Int Pharmacodyn 27: 201–217Google Scholar
  140. Suzuki H, Morita K, Kuriyama H (1976) Innervation and properties of the smooth muscle of the dog trachea. Jpn J Physiol 26: 303–320PubMedGoogle Scholar
  141. Takuwa Y, Takuwa N, Rasmussen H (1986) Carbachol induces a rapid and sustained hydrolysis of polyphosphoinositide in bovine tracheal smooth muscle. Measurements of the mass of polyphosphoinositides, 1,2-diacylglycerol and phosphatidic acid. J Biol Chem 261: 14670–14675PubMedGoogle Scholar
  142. Takuwa Y, Takuwa N, Rasmussen H (1987) Measurement of cytoplasmic free Ca2+ concentration in bovine tracheal smooth muscle using aequorin. Am J Physiol 253: C817–C827PubMedGoogle Scholar
  143. Takuwa Y, Takuwa N, Rasmussen H (1988) The effects of isoproterenol on intracellular calcium concentration. J Biol Chem 263: 762–768PubMedGoogle Scholar
  144. Taylor DA, Stull JT (1988) Calcium dependence of myosin light chain phosphorylation in smooth muscle cells. J Biol Chem 263: 14456–14462PubMedGoogle Scholar
  145. Taylor DA, Bowman BF, Stull JT (1989) Cytoplasmic Ca2+ is a primary determinant for myosin phosphorylation in smooth muscle cells. J Biol Chem 264: 6207–6213PubMedGoogle Scholar
  146. Thomas AP (1988) Enhancement of the inositol 1,4,5-trisphosphate-releasable Ca2+ pool by GTP in permeabilised hepatocytes. J Biol Chem 263: 2704–2711PubMedGoogle Scholar
  147. Torphy TJ (1988) Action of mediators on airway smooth muscle: functional antagonism as a mechanism for bronchodilator drugs. Agents Actions [Suppl] 23: 37–53Google Scholar
  148. Torphy TJ, Gerthoffer WT (1986) Biochemical mechansims of airway smooth muscle contraction and relaxation. In:Hollinger MA (ed) Current topics in pulmonary pharmacology and toxicology, vol 1. Elsevier, New York, pp 23–56Google Scholar
  149. Twort CHC, Van Breemen C (1989) Human airway smooth muscle in cell culture: control of the intracellular calcium store. Pulm Pharmacol 2: 45–53PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1991

Authors and Affiliations

  • I. W. Rodger
  • R. C. Small

There are no affiliations available

Personalised recommendations