Pharmacology of Calcium Metabolism in Smooth Muscle

  • T. Godfraind
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 83)


Calcium may be considered as the ultimate intracellular messenger of the signals received at the level of smooth muscle pericellular membrane to produce a change in the active tone. The calcium responsible for the increase in free cytoplasmic levels is potentially available from the intracellular space and also from several compartments having various affinities for calcium. Several cellular mechanisms maintain the calcium gradient across the plasmalemmal membrane. They are associated with the plasma membrane itself and with intracellular organelles. Differences between muscles are to some extent due to differences in the importance and the properties of the different mechanisms operating at rest and during activation. Pharmacologic agents influence calcium movements by acting on those mechanisms responsible for calcium homeostasis at the cellular level (Table 1). Understanding of the mode of action of those agents requires a proper analysis of the mechanisms of this calcium homeostasis.


Smooth Muscle Microsomal Fraction Calcium Entry Calcium Metabolism Entry Blocker 
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  1. Alosachie I, Godfraind T (1986) Role of cyclic GMP in the modulation by endothelium of the adrenolytic action of prazosin in rat isolated aorta. Br J Pharmacol 80:525–532Google Scholar
  2. Baker PF, Blaustein MP, Hodgkin AL, Steinhard RA (1969) The influence of Ca on Na efflux in squid axons. J Physiol (Lond) 200:431–458Google Scholar
  3. Batra S (1985) Characterization of [3H]-nitrendipine binding to uterine smooth muscle plasma membrane and its relevance to inhibition of calcium entry. Br J Pharmacol 85:767–774PubMedGoogle Scholar
  4. Bolger GT, Gengo PJ, Luchowski EM, Siegel H, Toggle DJ, Janis RA (1982) High affinity binding of a calcium channel antagonist to smooth and cardiac muscle. Biochem Biophys Res Commun 104:1604–1609PubMedCrossRefGoogle Scholar
  5. Bolger GT, Gengo P, Klockowski R, Luchowski E, Siegel H, Janis RA, Triggle AM, Triggle DJ (1983) Characterization of binding of the Ca++ channel antagonist, [3H]nitrendipine, to guinea-pig ileal smooth muscle. J Pharmacol Exp Ther 225:291–309PubMedGoogle Scholar
  6. Bolton TB (1979) Mechanisms of action of transmitters and other substances on smooth muscle. Physiol Rev 59:606–718PubMedGoogle Scholar
  7. Brading AF (1981) Ionic distribution and mechanism of transmembrane ion movements in smooth muscle. In: Bülbring EE, Brading AF, Jones AW, Tomita T (eds) Smooth muscle. Arnold, London, pp 65–92Google Scholar
  8. Broekaert A, Godfraind T (1979) A comparison of the inhibitory effect of cinnarizine and papaverine on the noradrenaline and calcium-evoked contraction of isolated rabbit aorta and mesenteric arteries. Eur J Pharmacol 53:281–288PubMedCrossRefGoogle Scholar
  9. Caroni P, Carafoli E (1983) The regulation of the Na+-Ca2+ exchanger of heart sarcolemma. Eur J Biochem 132:451–460PubMedCrossRefGoogle Scholar
  10. Caroni P, Reinlib L, Carafoli E (1980) Charge movements during the Na+-Ca2+ exchange in heart sarcolemmal vesicles. Proc Natl Acad Sci (USA) 77:6354–6358CrossRefGoogle Scholar
  11. Casteels R, van Breemen C (1975) Active and passive Ca2+ fluxes across cell membranes of the guinea-pig taenia coli. Pflügers Arch 359:197–207PubMedCrossRefGoogle Scholar
  12. Cauvin C, Saida K, van Breemen C (1982) Effects of Ca antagonists on Ca fluxes in resistance vessels. J Cardiovasc Pharmacol 4:S287–290PubMedCrossRefGoogle Scholar
  13. De Pover A, Matlib MA, Lee SW, Dube GP, Grupp IL, Grupp G, Schwartz A (1982) Specific binding [3H] nitrendipine to membranes from coronary arteries and heart in relation to pharmacological effects. Paradoxical stimulation by diltiazem. Biochem Biophys Res Commun 108:110–117CrossRefGoogle Scholar
  14. Egleme C, Godfraind T, Miller RC (1984) Enhanced responsiveness of rat isolated aorta to Clonidine after removal of the endothelial cell. Br J Pharmacol 81:16–18PubMedGoogle Scholar
  15. Fabiato A, Fabiato F (1979) Calcium and cardiac excitation contraction coupling. Ann Rev Physiol 41:473–484CrossRefGoogle Scholar
  16. Fleckenstein A (1973) Calcium antagonism in heart and smooth muscle. Wiley, New YorkGoogle Scholar
  17. Furchgott RF (1984) The role of endothelium in the responses of vascular smooth muscle to drugs. Ann Rev Pharmacol Toxicol 24:175–197CrossRefGoogle Scholar
  18. Godfraind T (1976) Calcium exchange in vascular smooth muscle, action of noradrenaline and lanthanum. J Physiol (Lond) 260:21–35Google Scholar
  19. Godfraind T (1983) Actions of nifedipine on calcium fluxes and contraction in isolated rat arteries. J Pharmacol Exp Ther 224:443–450PubMedGoogle Scholar
  20. Godfraind T (1985) Cellular and subcellular approaches to the mechanism of action of calcium antagonists. In: Rubin RP, Weiss GB, Putney JW (eds) Calcium in biological systems. Plenum, New York, pp 411–421CrossRefGoogle Scholar
  21. Godfraind T (1986 a) Calcium entry blockade and excitation contraction coupling in the cardiovascular systems (with an attempt of pharmacological classification). Acta Pharmacol Toxicol 58 (Suppl 2): 5–30CrossRefGoogle Scholar
  22. Godfraind T (1986 b) EDRF and cyclic GMP control gating of receptor-operated calcium channels in vascular smooth muscle. Eur J Pharmacol 126:341–343PubMedCrossRefGoogle Scholar
  23. Godfraind T, Dieu D (1981) The inhibition by fluanrizine on the norepinephrine evoked contraction and calcium influx in rat aorta and mesenteric arteries. J Pharmacol Exp Ther 217:510–515PubMedGoogle Scholar
  24. Godfraind T, Kaba A (1969) Blockade or reversal of contraction induced by calcium and adrenaline in depolarized arterial smooth muscle. Br J Pharmacol 36:549–560PubMedGoogle Scholar
  25. Godfraind T, Miller RC (1983) Specificity of action of Ca+ entry blockers. A comparison of their actions in rat arteries and in human coronary arteries. Circ Res 52 (Suppl 1):81–91Google Scholar
  26. Godfraind T, Polster P (1968) Etude comparative de médicaments inhibant la réponse contractile de vaisseaux isolés d’origine humaine et animale. Thérapie 23:1209–1220PubMedGoogle Scholar
  27. Godfraind T, Wibo M (1985) Subcellular localization of [3H]-nitrendipine binding sites in guinea-pig ileal smooth muscle. Br J Pharmacol 85:335–340PubMedGoogle Scholar
  28. Godfraind T, Kaba A, Polster P (1968) Differences in sensitivity of arterial smooth muscle to inhibition of their contractile response to depolarization by potassium. Arch Int Pharmacodyn Ther 172:235–239PubMedGoogle Scholar
  29. Goodfraind T, Finet M, Socrates Lima J, Miller R (1984) Contractile activity of human coronary arteries and human myocardium in vitro and their sensitivity to calcium entry blockade by nifedipine. J Pharmacol Exp Ther 230:514–518Google Scholar
  30. Godfraind T, Egleme C, Alosachie I (1985 a) Role of endothelium in the contractile response of rat aorta to alpha-adrenergic agonists. Clin Sci 68:65s–71sPubMedGoogle Scholar
  31. Godfraind T, Egleme C, Wibo M (1985 b) Effects of dihydropyridines on human and animal isolated vessels. In: Fleckenstein A, Breemen C van, Gross R, Hoffmeister F (eds) Cardiovascular effects of dihydropyridine-type calcium antagonists and agonists. Springer, Berlin Heidelberg New York Tokyo, pp 309–325 (Bayer symposium, vol 9)CrossRefGoogle Scholar
  32. Godfraind T, Miller RC, Wibo M (1986) Calcium antagonism and calcium entry blockade. Pharmacol Rev 38:321–416PubMedGoogle Scholar
  33. Godfraind-De Becker A, Godfraind T (1980) Calcium transport system: a comparative study in different cells. Int Rev Cytol 67:141–170PubMedCrossRefGoogle Scholar
  34. Grover AK, Oakes PJ (1985) Calcium channel antagonist binding and pharmacology in rat uterine smooth muscle. Life Sci 37:2187–2192PubMedCrossRefGoogle Scholar
  35. Hidaka H, Hartshorne DJ (1985) Calmodulin antagonists and cellular physiology. Academic, Orlando, p 543Google Scholar
  36. Hirata M, Itoh T, Kuriyama H (1981) Effects of external cations on calcium efflux from single cells of guinea-pig taenia coli and porcine coronary artery. J Physiol (Lond) 310:321–336Google Scholar
  37. Jim K, Harris A, Rosenberger LB, Triggle DJ (1981) Stereoselective and non-stereoselective effects of D 600 (methoxyverapamil) in smooth muscle preparations. Eur J Pharmacol 76:67–72PubMedCrossRefGoogle Scholar
  38. Lincoln TM (1983) Effects of nitroprusside and 8-bromo-cyclic GMP on the contractile activity of the rat aorta. J Pharmacol Exp Ther 224:100–107PubMedGoogle Scholar
  39. Meisheri KD, van Breemen C (1982) Effects of beta-adrenergic stimulation on calcium movements in rabbit aortic smooth muscle: relation with cyclic AMP. J Physiol (Lond) 331:429–441Google Scholar
  40. Meisheri KD, Hwang O, van Breemen C (1981) Evidence for two separate Ca2+ pathways in smooth muscle-plasmalemma. J Membr Biol 59:19–25PubMedCrossRefGoogle Scholar
  41. Morel N, Godfraind T (1982) Na-Ca exchange in heart and smooth muscle microsomes. Arch Int Pharmacodyn Ther 258:319–321PubMedGoogle Scholar
  42. Morel N, Godfraind T (1984) Sodium/Calcium exchange in smooth-muscle microsomal fractions. Biochem J 218:421–427PubMedGoogle Scholar
  43. Morel N, Wibo M, Godfraind T (1981) A calmodulin-stimulated Ca2+ pump in rat aorta plasma membranes. Biochim Biophys Acta 644:82–88PubMedCrossRefGoogle Scholar
  44. Philipson KD, Nishimoto AY (1980) Na+-Ca2+ exchange is affected by membrane potential in cardiac sarcolemmal vesicles. J Biol Chem 255:6880–6882PubMedGoogle Scholar
  45. Pitts BJ (1979) Stoichiometry of sodium-calcium exchange in cardiac sarcolemmal vesicles. J Biol Chem 254:6232–6235PubMedGoogle Scholar
  46. Reeves JP, Sutko JL (1979) Sodium-calcium ion exchange in cardiac membrane vesicles. Proc Natl Acad Sci (USA) 76:590–594CrossRefGoogle Scholar
  47. Reuter H (1974) Exchange of calcium ions in the mammalian myocardium. Mechanisms and physiological significance. Circ Res 34:599–609PubMedGoogle Scholar
  48. Reuter H (1982) Na-Ca countertransport in cardiac muscle. In: Martonosi A (ed) Membrane and transport, vol 1. Plenum, New York, pp 623–631Google Scholar
  49. Saida K, van Breemen C (1983) Mechanism of Ca2+ antagonist-induced vasodilation. Intracellular actions. Circ Res 52:137–142PubMedGoogle Scholar
  50. Schatzmann HJ, Vincenzi FF (1969) Calcium movements across the membrane of human red cells. J Physiol (Lond) 201:369Google Scholar
  51. Schramm M, Thomas G, Towart R, Franckowiak G (1983) Novel dihydropyridines with positive inotropic action through activation of Ca2+ channels. Nature 303:535–537PubMedCrossRefGoogle Scholar
  52. Somlyo AV, Bond M, Somloy AP, Scarpa A (1985) Inositol trisphosphate-induced calcium release and contraction in vascular smooth muscle. Proc Natl Acad Sci USA 82:5231PubMedCrossRefGoogle Scholar
  53. Suematsu E, Hirata M, Hashimoto T, Kuriyama H (1984) Inositol 1,4,5-trisphosphate releases Ca2+ from intracellular store sites in skinned single cells of porcine coronary artery. Biochem Biophys Res Commun 120:481PubMedCrossRefGoogle Scholar
  54. Triggle CR, Agrawal DK, Bolger GT, Daniel EE, Kwan CY, Luchowski EM, Triggle DJ (1982) Calcium channel antagonist binding to isolated vascular smooth muscle membranes. Can J Physiol Pharmacol 60:1738–1741PubMedCrossRefGoogle Scholar
  55. Van Nueten JM (1982) Selectivity of calcium entry blockers. In: Godfraind T, Albertini A, Paoletti R (eds) Calcium modulators. Elsevier, Amsterdam, pp 199–208Google Scholar
  56. Venter JC, Fraser CM, Schaber JS, Jung CY, Bolger S, Triggle DJ (1983) Molecular properties of the slow inward calcium channel. Molecular weight determinations by radiation inactivation and covalent affinity labeling. J Biol Chem 258:9344–9348PubMedGoogle Scholar
  57. Wibo M, Morel N, Godfraind T (1981) Differentiation of Ca2+ pumps linked to plasma membrane and endoplasmic reticulum in the microsomal fraction from intestinal smooth muscle. Biochim Biophys Acta 649:651–660PubMedCrossRefGoogle Scholar
  58. Williams JA (1980) Regulation of pancreatic acinar cell function by intracellular calcium. Am J Physiol 238:G269–G279PubMedGoogle Scholar
  59. Winquist RJ (1984) Modulators of intracellular calcium. Drug Dev Res 4:241–256CrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1988

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  • T. Godfraind

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