Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Sep;119(1):142–148. doi: 10.1111/j.1476-5381.1996.tb15687.x

The effect of L-type calcium channel modulators on the mobilization of intracellular calcium stores in guinea-pig intestinal smooth muscle.

C Dessy 1, T Godfraind 1
PMCID: PMC1915731  PMID: 8872367

Abstract

1. The action of Ca2+ channel modulators has been examined on the intracellular Ca2+ signal in the longitudinal smooth muscle cells of the guinea-pig intestine after exposure to histamine and to agents known to affect intracellular Ca2+ stores. Isometric contraction has been measured simultaneously with front-surface fluorometry of fura 2-loaded preparations. 2. Histamine (10 microM) evoked a phasic and tonic increase in [Ca2+]i and contraction which were both sensitive to the Ca2+ channel blockers, nimodipine and D600. 3. Caffeine (10 mM) evoked in rapid increase in [Ca2+]i which was sustained as long as the preparation was exposed to the drug, whereas the contractile response was only phasic. In the presence of nimodipine 1 microM, the phasic contraction was absent although the fura 2-Ca2+ signal amounted to 32% of the control. 4. Ryanodine (10 microM) evoked a slow increase in [Ca2+]i and a contraction, both of which were reversed after exposure to nimodipine (1 microM) or D600 (10 microM). In the presence of diazoxide (500 microM), a hyperpolarizing agent, the ryanodine-evoked increase in [Ca2+]i and in muscle tone were inhibited. 5. Thapsigargin (1 microM) also produced an increase in [Ca2+]i and a contraction both of which were blocked by nimodipine (1 microM). 6. In Ca2+-free solution, histamine 10 microM evoked non-reproducible phasic Ca2+ signal and contraction. This response was recovered after refilling in Ca2+ containing solution. The recovery was blocked by nimodipine, D600 or diazoxide and was facilitated by the Ca2+ channel activator, Bay K 8644. When the refilling medium was supplemented with thapsigargin, the recovered response was significantly reduced, but Bay K 8644 still had some action. 7. The present results show that blockage of L-type Ca2+ channels inhibited changes in [Ca2+]i evoked by histamine, caffeine and ryanodine which are generally attributed to Ca2+ mobilization from intracellular stores. They also show that when the tissue was exposed to nimodipine, D600 and diazoxide during the procedure of refilling after depletion of intracellular stores, the action of histamine on [Ca2+]i and contraction was blocked. Bay K 8644 had an opposite effect even when the Ca2+ pumping activity of the sarcoplasmic reticulum was reduced by thapsigargin. This indicates that refilling of intracellular Ca2+ stores depleted by histamine in guinea-pig intestine mainly occurred through L-type Ca2+ channels.

Full text

PDF
147

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Antoine M. H., Berkenboom G., Fang Z. Y., Fontaine J., Herchuelz A., Lebrun P. Mechanical and ionic response of rat aorta to diazoxide. Eur J Pharmacol. 1992 Jun 5;216(2):299–306. doi: 10.1016/0014-2999(92)90374-d. [DOI] [PubMed] [Google Scholar]
  2. Ashida T., Schaeffer J., Goldman W. F., Wade J. B., Blaustein M. P. Role of sarcoplasmic reticulum in arterial contraction: comparison of ryanodines's effect in a conduit and a muscular artery. Circ Res. 1988 Apr;62(4):854–863. doi: 10.1161/01.res.62.4.854. [DOI] [PubMed] [Google Scholar]
  3. Buryi V., Morel N., Salomone S., Kerger S., Godfraind T. Evidence for a direct interaction of thapsigargin with voltage-dependent Ca2+ channel. Naunyn Schmiedebergs Arch Pharmacol. 1995 Jan;351(1):40–45. doi: 10.1007/BF00169062. [DOI] [PubMed] [Google Scholar]
  4. Casteels R., Raeymaekers L. The action of acetylcholine and catecholamines on an intracellular calcium store in the smooth muscle cells of the guinea-pig taenia coli. J Physiol. 1979 Sep;294:51–68. doi: 10.1113/jphysiol.1979.sp012914. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chen Q., van Breemen C. The superficial buffer barrier in venous smooth muscle: sarcoplasmic reticulum refilling and unloading. Br J Pharmacol. 1993 Jun;109(2):336–343. doi: 10.1111/j.1476-5381.1993.tb13575.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Donaldson J., Hill S. J. Histamine-induced inositol phospholipid breakdown in the longitudinal smooth muscle of guinea-pig ileum. Br J Pharmacol. 1985 Jun;85(2):499–512. doi: 10.1111/j.1476-5381.1985.tb08887.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Endo M., Yagi S., Iino M. Tension-pCa relation and sarcoplasmic reticulum responses in chemically skinned smooth muscle fibers. Fed Proc. 1982 May;41(7):2245–2250. [PubMed] [Google Scholar]
  8. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  9. Himpens B., Somlyo A. P. Free-calcium and force transients during depolarization and pharmacomechanical coupling in guinea-pig smooth muscle. J Physiol. 1988 Jan;395:507–530. doi: 10.1113/jphysiol.1988.sp016932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hisayama T., Takayanagi I., Okamoto Y. Ryanodine reveals multiple contractile and relaxant mechanisms in vascular smooth muscle: simultaneous measurements of mechanical activity and of cytoplasmic free Ca2+ level with fura-2. Br J Pharmacol. 1990 Aug;100(4):677–684. doi: 10.1111/j.1476-5381.1990.tb14075.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hwang K. S., van Breemen C. Ryanodine modulation of 45Ca efflux and tension in rabbit aortic smooth muscle. Pflugers Arch. 1987 Apr;408(4):343–350. doi: 10.1007/BF00581127. [DOI] [PubMed] [Google Scholar]
  12. Iino M., Kobayashi T., Endo M. Use of ryanodine for functional removal of the calcium store in smooth muscle cells of the guinea-pig. Biochem Biophys Res Commun. 1988 Apr 15;152(1):417–422. doi: 10.1016/s0006-291x(88)80730-7. [DOI] [PubMed] [Google Scholar]
  13. Itoh T., Kuriyama H., Suzuki H. Differences and similarities in the noradrenaline- and caffeine-induced mechanical responses in the rabbit mesenteric artery. J Physiol. 1983 Apr;337:609–629. doi: 10.1113/jphysiol.1983.sp014645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Julou-Schaeffer G., Freslon J. L. Effects of ryanodine on tension development in rat aorta and mesenteric resistance vessels. Br J Pharmacol. 1988 Oct;95(2):605–613. doi: 10.1111/j.1476-5381.1988.tb11682.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kanmura Y., Missiaen L., Raeymaekers L., Casteels R. Ryanodine reduces the amount of calcium in intracellular stores of smooth-muscle cells of the rabbit ear artery. Pflugers Arch. 1988 Dec;413(2):153–159. doi: 10.1007/BF00582525. [DOI] [PubMed] [Google Scholar]
  16. Low A. M., Kwan C. Y., Daniel E. E. Evidence for two types of internal Ca2+ stores in canine mesenteric artery with different refilling mechanisms. Am J Physiol. 1992 Jan;262(1 Pt 2):H31–H37. doi: 10.1152/ajpheart.1992.262.1.H31. [DOI] [PubMed] [Google Scholar]
  17. Lynn S., Morgan J. M., Gillespie J. I., Greenwell J. R. A novel ryanodine sensitive calcium release mechanism in cultured human myometrial smooth-muscle cells. FEBS Lett. 1993 Sep 13;330(2):227–230. doi: 10.1016/0014-5793(93)80279-4. [DOI] [PubMed] [Google Scholar]
  18. Morel N., Hardy J. P., Godfraind T. Histamine-operated calcium channels in intestinal smooth muscle of the guinea-pig. Eur J Pharmacol. 1987 Mar 3;135(1):69–75. doi: 10.1016/0014-2999(87)90758-8. [DOI] [PubMed] [Google Scholar]
  19. Newgreen D. T., Bray K. M., McHarg A. D., Weston A. H., Duty S., Brown B. S., Kay P. B., Edwards G., Longmore J., Southerton J. S. The action of diazoxide and minoxidil sulphate on rat blood vessels: a comparison with cromakalim. Br J Pharmacol. 1990 Jul;100(3):605–613. doi: 10.1111/j.1476-5381.1990.tb15854.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ohta T., Kawai K., Ito S., Nakazato Y. Ca2+ entry activated by emptying of intracellular Ca2+ stores in ileal smooth muscle of the rat. Br J Pharmacol. 1995 Mar;114(6):1165–1170. doi: 10.1111/j.1476-5381.1995.tb13329.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Prestwich S. A., Bolton T. B. Inhibition of muscarinic receptor-induced inositol phospholipid hydrolysis by caffeine, beta-adrenoceptors and protein kinase C in intestinal smooth muscle. Br J Pharmacol. 1995 Feb;114(3):602–611. doi: 10.1111/j.1476-5381.1995.tb17182.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Putney J. W., Jr Capacitative calcium entry revisited. Cell Calcium. 1990 Nov-Dec;11(10):611–624. doi: 10.1016/0143-4160(90)90016-n. [DOI] [PubMed] [Google Scholar]
  23. Quast U. Potassium channel openers: pharmacological and clinical aspects. Fundam Clin Pharmacol. 1992;6(7):279–293. doi: 10.1111/j.1472-8206.1992.tb00122.x. [DOI] [PubMed] [Google Scholar]
  24. Rembold C. M., Van Riper D. A., Chen X. L. Focal [Ca2+]i increases detected by aequorin but not by fura-2 in histamine- and caffeine-stimulated swine carotid artery. J Physiol. 1995 Nov 1;488(Pt 3):549–564. doi: 10.1113/jphysiol.1995.sp020989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Sato K., Sanders K. M., Gerthoffer W. T., Publicover N. G. Sources of calcium utilized in cholinergic responses in canine colonic smooth muscle. Am J Physiol. 1994 Dec;267(6 Pt 1):C1666–C1673. doi: 10.1152/ajpcell.1994.267.6.C1666. [DOI] [PubMed] [Google Scholar]
  26. Shima H., Blaustein M. P. Modulation of evoked contractions in rat arteries by ryanodine, thapsigargin, and cyclopiazonic acid. Circ Res. 1992 May;70(5):968–977. doi: 10.1161/01.res.70.5.968. [DOI] [PubMed] [Google Scholar]
  27. Wagner-Mann C., Hu Q., Sturek M. Multiple effects of ryanodine on intracellular free Ca2+ in smooth muscle cells from bovine and porcine coronary artery: modulation of sarcoplasmic reticulum function. Br J Pharmacol. 1992 Apr;105(4):903–911. doi: 10.1111/j.1476-5381.1992.tb09076.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Watanabe C., Yamamoto H., Hirano K., Kobayashi S., Kanaide H. Mechanisms of caffeine-induced contraction and relaxation of rat aortic smooth muscle. J Physiol. 1992 Oct;456:193–213. doi: 10.1113/jphysiol.1992.sp019333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Watson S. P., Stanley A. F., Sasaguri T. Does the hydrolysis of inositol phospholipids lead to the opening of voltage operated Ca2+ channels in guinea-pig ileum? Studies with fluoride ions and caffeine. Biochem Biophys Res Commun. 1988 May 31;153(1):14–20. doi: 10.1016/s0006-291x(88)81183-5. [DOI] [PubMed] [Google Scholar]
  30. Wibo M., Godfraind T. Comparative localization of inositol 1,4,5-trisphosphate and ryanodine receptors in intestinal smooth muscle: an analytical subfractionation study. Biochem J. 1994 Jan 15;297(Pt 2):415–423. doi: 10.1042/bj2970415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wong A. Y., Klassen G. A. A model of calcium regulation in smooth muscle cell. Cell Calcium. 1993 Mar;14(3):227–243. doi: 10.1016/0143-4160(93)90070-m. [DOI] [PubMed] [Google Scholar]
  32. Xuan Y. T., Wang O. L., Whorton A. R. Thapsigargin stimulates Ca2+ entry in vascular smooth muscle cells: nicardipine-sensitive and -insensitive pathways. Am J Physiol. 1992 May;262(5 Pt 1):C1258–C1265. doi: 10.1152/ajpcell.1992.262.5.C1258. [DOI] [PubMed] [Google Scholar]
  33. Yamazawa T., Iino M., Endo M. Presence of functionally different compartments of the Ca2+ store in single intestinal smooth muscle cells. FEBS Lett. 1992 Apr 20;301(2):181–184. doi: 10.1016/0014-5793(92)81243-f. [DOI] [PubMed] [Google Scholar]
  34. Zhang G. H., Melvin J. E. Inhibitors of the intracellular Ca2+ release mechanism prevent muscarinic-induced Ca2+ influx in rat sublingual mucous acini. FEBS Lett. 1993 Jul 19;327(1):1–6. doi: 10.1016/0014-5793(93)81026-v. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES