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. 1992;451:307–328. doi: 10.1113/jphysiol.1992.sp019166

Membrane hyperpolarization inhibits agonist-induced synthesis of inositol 1,4,5-trisphosphate in rabbit mesenteric artery.

T Itoh 1, N Seki 1, S Suzuki 1, S Ito 1, J Kajikuri 1, H Kuriyama 1
PMCID: PMC1176163  PMID: 1328618

Abstract

1. Effects of membrane hyperpolarization induced by pinacidil on Ca2+ mobilization induced by noradrenaline (NA) were investigated by measuring intracellular Ca2+ concentration ([Ca2+]i), isometric tension, membrane potential and production of inositol 1,4,5-trisphosphate (IP3) in smooth muscle cells of the rabbit mesenteric artery. 2. Pinacidil (0.1-10 microM) concentration dependently hyperpolarized the smooth muscle membrane with a reduction in membrane resistance. Glibenclamide (1 microM) blocked the membrane hyperpolarization induced by 1 microM-pinacidil. NA (10 microM) depolarized the smooth muscle membrane with associated oscillations. Pinacidil (1 microM) inhibited this response and glibenclamide (1 microM) prevented the action of pinacidil on both the NA-induced events. 3. In thin smooth muscle strips, 10 microM-NA produced a large phasic and a subsequent small tonic increase in [Ca2+]i with associated oscillations. These changes in [Ca2+]i seemed to be coincident with phasic, tonic and oscillatory contractions, respectively. Pinacidil (0.1-1 microM) inhibited the increases in [Ca2+]i and in tension induced by NA, but not by 128 mM-K+. Glibenclamide inhibited these actions of pinacidil. Pinacidil (1 microM) also inhibited the contraction induced by 10 microM-NA in strips treated with A23187 (which functionally removes cellular Ca2+ storage sites), suggesting that membrane hyperpolarization inhibits Ca2+ influxes activated by NA. 4. In Ca2(+)-free solution containing 2 mM-EGTA, NA (10 microM) transiently increased [Ca2+]i, tension and synthesis of IP3. Pinacidil (over 0.1 microM) inhibited the increases in [Ca2+]i, tension and synthesis of IP3 induced by 10 microM-NA in Ca2(+)-free solution containing 5.9 mM-K+, but not in a similar solution containing 40 or 128 mM-K+. Glibenclamide (1 microM) inhibited these actions of pinacidil. These inhibitory actions of pinacidil were still observed in solutions containing low Na+ or low Cl-. These results suggest that pinacidil inhibits NA-induced Ca2+ release from storage sites through an inhibition of IP3 synthesis resulting from its membrane hyperpolarizing action. 5. In beta-escin-treated skinned strips, NA (10 microM) or IP3 (20 microM) increased Ca2+ in Ca2(+)-free solution containing 50 microM-EGTA and 3 microM-guanosine triphosphate (GTP) after brief application of 0.3 microM-Ca2+, suggesting Ca2+ is released from intracellular storage sites. Heparin (500 micrograms/ml, an inhibitor of the IP3 receptor), but not pinacidil (1 microM) or glibenclamide (1 microM), inhibited the Ca2+ release from storage sites induced by NA or IP3. These results suggest that membrane hyperpolarization is essential for the inhibitory action of pinacidil on the NA-induced Ca2(+)-releasing mechanism.(ABSTRACT TRUNCATED AT 400 WORDS)

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Selected References

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  1. Abe Y., Tomita T. Cable properties of smooth muscle. J Physiol. 1968 May;196(1):87–100. doi: 10.1113/jphysiol.1968.sp008496. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anabuki J., Hori M., Ozaki H., Kato I., Karaki H. Mechanisms of pinacidil-induced vasodilatation. Eur J Pharmacol. 1990 Nov 13;190(3):373–379. doi: 10.1016/0014-2999(90)94202-9. [DOI] [PubMed] [Google Scholar]
  3. Ashcroft F. M. Adenosine 5'-triphosphate-sensitive potassium channels. Annu Rev Neurosci. 1988;11:97–118. doi: 10.1146/annurev.ne.11.030188.000525. [DOI] [PubMed] [Google Scholar]
  4. Becker P. L., Singer J. J., Walsh J. V., Jr, Fay F. S. Regulation of calcium concentration in voltage-clamped smooth muscle cells. Science. 1989 Apr 14;244(4901):211–214. doi: 10.1126/science.2704996. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. Hashimoto T., Hirata M., Itoh T., Kanmura Y., Kuriyama H. Inositol 1,4,5-trisphosphate activates pharmacomechanical coupling in smooth muscle of the rabbit mesenteric artery. J Physiol. 1986 Jan;370:605–618. doi: 10.1113/jphysiol.1986.sp015953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Ito S., Kajikuri J., Itoh T., Kuriyama H. Effects of lemakalim on changes in Ca2+ concentration and mechanical activity induced by noradrenaline in the rabbit mesenteric artery. Br J Pharmacol. 1991 Sep;104(1):227–233. doi: 10.1111/j.1476-5381.1991.tb12411.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Itoh T., Kanmura Y., Kuriyama H. A23187 increases calcium permeability of store sites more than of surface membranes in the rabbit mesenteric artery. J Physiol. 1985 Feb;359:467–484. doi: 10.1113/jphysiol.1985.sp015597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Itoh T., Kanmura Y., Kuriyama H. Inorganic phosphate regulates the contraction-relaxation cycle in skinned muscles of the rabbit mesenteric artery. J Physiol. 1986 Jul;376:231–252. doi: 10.1113/jphysiol.1986.sp016151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Itoh T., Kubota Y., Kuriyama H. Effects of a phorbol ester on acetylcholine-induced Ca2+ mobilization and contraction in the porcine coronary artery. J Physiol. 1988 Mar;397:401–419. doi: 10.1113/jphysiol.1988.sp017008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. Itoh T., Suzuki S., Kuriyama H. Effects of pinacidil on contractile proteins in high K(+)-treated intact, and in beta-escin-treated skinned smooth muscle of the rabbit mesenteric artery. Br J Pharmacol. 1991 Jul;103(3):1697–1702. doi: 10.1111/j.1476-5381.1991.tb09849.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kajikuri J., Kuriyama H. Inhibitory action of alpha-human atrial natriuretic peptide on noradrenaline-induced synthesis of myo-inositol 1,4,5-trisphosphate in the smooth muscle cells of rabbit aorta. Br J Pharmacol. 1990 Mar;99(3):536–540. doi: 10.1111/j.1476-5381.1990.tb12964.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kanmura Y., Itoh T., Suzuki H., Ito Y., Kuriyama H. Effects of nifedipine on smooth muscle cells of the rabbit mesenteric artery. J Pharmacol Exp Ther. 1983 Jul;226(1):238–248. [PubMed] [Google Scholar]
  15. Kitazawa T., Kobayashi S., Horiuti K., Somlyo A. V., Somlyo A. P. Receptor-coupled, permeabilized smooth muscle. Role of the phosphatidylinositol cascade, G-proteins, and modulation of the contractile response to Ca2+. J Biol Chem. 1989 Apr 5;264(10):5339–5342. [PubMed] [Google Scholar]
  16. Kobayashi S., Kitazawa T., Somlyo A. V., Somlyo A. P. Cytosolic heparin inhibits muscarinic and alpha-adrenergic Ca2+ release in smooth muscle. Physiological role of inositol 1,4,5-trisphosphate in pharmacomechanical coupling. J Biol Chem. 1989 Oct 25;264(30):17997–18004. [PubMed] [Google Scholar]
  17. Konishi M., Olson A., Hollingworth S., Baylor S. M. Myoplasmic binding of fura-2 investigated by steady-state fluorescence and absorbance measurements. Biophys J. 1988 Dec;54(6):1089–1104. doi: 10.1016/S0006-3495(88)83045-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Lang D., Lewis M. J. Endothelium-derived relaxing factor inhibits the formation of inositol trisphosphate by rabbit aorta. J Physiol. 1989 Apr;411:45–52. doi: 10.1113/jphysiol.1989.sp017558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Makita Y., Kanmura Y., Itoh T., Suzuki H., Kuriyama H. Effects of nifedipine derivatives on smooth muscle cells and neuromuscular transmission in the rabbit mesenteric artery. Naunyn Schmiedebergs Arch Pharmacol. 1983 Dec;324(4):302–312. doi: 10.1007/BF00502628. [DOI] [PubMed] [Google Scholar]
  20. Mishima S., Miyahara H., Suzuki H. Transmitter release modulated by alpha-adrenoceptor antagonists in the rabbit mesenteric artery: a comparison between noradrenaline outflow and electrical activity. Br J Pharmacol. 1984 Oct;83(2):537–547. doi: 10.1111/j.1476-5381.1984.tb16518.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nakashima M., Li Y., Seki N., Kuriyama H. Pinacidil inhibits neuromuscular transmission indirectly in the guinea-pig and rabbit mesenteric arteries. Br J Pharmacol. 1990 Nov;101(3):581–586. doi: 10.1111/j.1476-5381.1990.tb14124.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nishimura J., van Breemen C. Direct regulation of smooth muscle contractile elements by second messengers. Biochem Biophys Res Commun. 1989 Sep 15;163(2):929–935. doi: 10.1016/0006-291x(89)92311-5. [DOI] [PubMed] [Google Scholar]
  23. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  24. Poenie M., Alderton J., Steinhardt R., Tsien R. Calcium rises abruptly and briefly throughout the cell at the onset of anaphase. Science. 1986 Aug 22;233(4766):886–889. doi: 10.1126/science.3755550. [DOI] [PubMed] [Google Scholar]
  25. Quast U., Cook N. S. Moving together: K+ channel openers and ATP-sensitive K+ channels. Trends Pharmacol Sci. 1989 Nov;10(11):431–435. doi: 10.1016/S0165-6147(89)80003-3. [DOI] [PubMed] [Google Scholar]
  26. Rapoport R. M. Cyclic guanosine monophosphate inhibition of contraction may be mediated through inhibition of phosphatidylinositol hydrolysis in rat aorta. Circ Res. 1986 Mar;58(3):407–410. doi: 10.1161/01.res.58.3.407. [DOI] [PubMed] [Google Scholar]
  27. Southerton J. S., Weston A. H., Bray K. M., Newgreen D. T., Taylor S. G. The potassium channel opening action of pinacidil; studies using biochemical, ion flux and microelectrode techniques. Naunyn Schmiedebergs Arch Pharmacol. 1988 Sep;338(3):310–318. doi: 10.1007/BF00173406. [DOI] [PubMed] [Google Scholar]
  28. Standen N. B., Quayle J. M., Davies N. W., Brayden J. E., Huang Y., Nelson M. T. Hyperpolarizing vasodilators activate ATP-sensitive K+ channels in arterial smooth muscle. Science. 1989 Jul 14;245(4914):177–180. doi: 10.1126/science.2501869. [DOI] [PubMed] [Google Scholar]
  29. Videbaek L. M., Aalkjaer C., Mulvany M. J. Pinacidil opens K+-selective channels causing hyperpolarization and relaxation of noradrenaline contractions in rat mesenteric resistance vessels. Br J Pharmacol. 1988 Sep;95(1):103–108. doi: 10.1111/j.1476-5381.1988.tb16553.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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