Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1996 Apr;117(7):1544–1548. doi: 10.1111/j.1476-5381.1996.tb15319.x

Inhibition by SK&F96365 of NO-mediated relaxation induced by Ca2(+) -ATPase inhibitors in rat thoracic aorta.

H Moritoki 1, T Hisayama 1, S Takeuchi 1, W Kondoh 1, S Inoue 1, K Kida 1
PMCID: PMC1909439  PMID: 8730752

Abstract

1. We investigated the effect of SK&F96365, a putative inhibitor of receptor-operated Ca2+ entry, on the endothelium-dependent, NO-mediated relaxation and cyclic GMP formation induced by Ca2(+)-ATPase inhibitors in rat thoracic aorta. 2. SK&F96365 inhibited cyclopiazonic acid or thapsigargin-induced relaxation and cyclic GMP formation mediated by a constitutive NO synthase, which is known to be activated by the Ca2+ that enters into the endothelial cells via plasma membrane Ca2+ channels subsequent to depletion of stored Ca2+ by Ca2(+)-ATPase inhibitors. 3. SK&F96365 also inhibited relaxation and cyclic GMP formation induced by acetylcholine, without affecting those induced by nitroprusside and A23187. 4. Ni2+ attenuated relaxation and cyclic GMP formation induced by cyclopiazonic acid and acetylcholine. 5. In contrast, the voltage-dependent Ca2+ channel blocker, nifedipine, did not affect the relaxation caused by Ca2(+)-ATPase inhibitors. 6. These results suggest that endothelium-dependent, NO-mediated relaxation of the arteries induced by Ca2(+)-ATPase inhibitors is triggered by the Ca2+ that enters into endothelial cells via receptor-operated channels (SK&F96365-sensitive channels) subsequent to depletion of stored Ca2+ as a result of inhibition of the Ca2(+)-ATPase (Ca2+ pump) of the stores.

Full text

PDF
1544

Selected References

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

  1. Adeagbo A. S., Triggle C. R. Effects of some inorganic divalent cations and protein kinase C inhibitors on endothelium-dependent relaxation in rat isolated aorta and mesenteric arteries. J Cardiovasc Pharmacol. 1991 Oct;18(4):511–521. doi: 10.1097/00005344-199110000-00006. [DOI] [PubMed] [Google Scholar]
  2. Colden-Stanfield M., Schilling W. P., Ritchie A. K., Eskin S. G., Navarro L. T., Kunze D. L. Bradykinin-induced increases in cytosolic calcium and ionic currents in cultured bovine aortic endothelial cells. Circ Res. 1987 Nov;61(5):632–640. doi: 10.1161/01.res.61.5.632. [DOI] [PubMed] [Google Scholar]
  3. Demaurex N., Lew D. P., Krause K. H. Cyclopiazonic acid depletes intracellular Ca2+ stores and activates an influx pathway for divalent cations in HL-60 cells. J Biol Chem. 1992 Feb 5;267(4):2318–2324. [PubMed] [Google Scholar]
  4. Demirel E., Laskey R. E., Purkerson S., van Breemen C. The passive calcium leak in cultured porcine aortic endothelial cells. Biochem Biophys Res Commun. 1993 Mar 31;191(3):1197–1203. doi: 10.1006/bbrc.1993.1344. [DOI] [PubMed] [Google Scholar]
  5. Dolor R. J., Hurwitz L. M., Mirza Z., Strauss H. C., Whorton A. R. Regulation of extracellular calcium entry in endothelial cells: role of intracellular calcium pool. Am J Physiol. 1992 Jan;262(1 Pt 1):C171–C181. doi: 10.1152/ajpcell.1992.262.1.C171. [DOI] [PubMed] [Google Scholar]
  6. Gericke M., Droogmans G., Nilius B. Thapsigargin discharges intracellular calcium stores and induces transmembrane currents in human endothelial cells. Pflugers Arch. 1993 Mar;422(6):552–557. doi: 10.1007/BF00374001. [DOI] [PubMed] [Google Scholar]
  7. Graier W. F., Groschner K., Schmidt K., Kukovetz W. R. SK&F 96365 inhibits histamine-induced formation of endothelium-derived relaxing factor in human endothelial cells. Biochem Biophys Res Commun. 1992 Aug 14;186(3):1539–1545. doi: 10.1016/s0006-291x(05)81582-7. [DOI] [PubMed] [Google Scholar]
  8. Hallam T. J., Jacob R., Merritt J. E. Influx of bivalent cations can be independent of receptor stimulation in human endothelial cells. Biochem J. 1989 Apr 1;259(1):125–129. doi: 10.1042/bj2590125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hallam T. J., Rink T. J. Agonists stimulate divalent cation channels in the plasma membrane of human platelets. FEBS Lett. 1985 Jul 8;186(2):175–179. doi: 10.1016/0014-5793(85)80703-1. [DOI] [PubMed] [Google Scholar]
  10. Inazu M., Zhang H., Daniel E. E. Different mechanisms can activate Ca2+ entrance via cation currents in endothelial cells. Life Sci. 1995;56(1):11–17. doi: 10.1016/0024-3205(94)00402-e. [DOI] [PubMed] [Google Scholar]
  11. Jacob R. Agonist-stimulated divalent cation entry into single cultured human umbilical vein endothelial cells. J Physiol. 1990 Feb;421:55–77. doi: 10.1113/jphysiol.1990.sp017933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jayakody R. L., Kappagoda C. T., Senaratne M. P., Sreeharan N. Absence of effect of calcium antagonists on endothelium-dependent relaxation in rabbit aorta. Br J Pharmacol. 1987 May;91(1):155–164. doi: 10.1111/j.1476-5381.1987.tb08994.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Johns A., Lategan T. W., Lodge N. J., Ryan U. S., Van Breemen C., Adams D. J. Calcium entry through receptor-operated channels in bovine pulmonary artery endothelial cells. Tissue Cell. 1987;19(6):733–745. doi: 10.1016/0040-8166(87)90015-2. [DOI] [PubMed] [Google Scholar]
  14. Krautwurst D., Hescheler J., Arndts D., Lösel W., Hammer R., Schultz G. Novel potent inhibitor of receptor-activated nonselective cation currents in HL-60 cells. Mol Pharmacol. 1993 May;43(5):655–659. [PubMed] [Google Scholar]
  15. Merritt J. E., Armstrong W. P., Benham C. D., Hallam T. J., Jacob R., Jaxa-Chamiec A., Leigh B. K., McCarthy S. A., Moores K. E., Rink T. J. SK&F 96365, a novel inhibitor of receptor-mediated calcium entry. Biochem J. 1990 Oct 15;271(2):515–522. doi: 10.1042/bj2710515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Moritoki H., Hisayama T., Kondoh W., Takeuchi S. Thapsigargin, a Ca(2+)-ATPase inhibitor, relaxes rat aorta via nitric oxide formation. Life Sci. 1994;54(9):PL153–PL158. doi: 10.1016/0024-3205(94)00875-2. [DOI] [PubMed] [Google Scholar]
  17. Moritoki H., Hisayama T., Takeuchi S., Kondoh W., Imagawa M. Relaxation of rat thoracic aorta induced by the Ca(2+)-ATPase inhibitor, cyclopiazonic acid, possibly through nitric oxide formation. Br J Pharmacol. 1994 Mar;111(3):655–662. doi: 10.1111/j.1476-5381.1994.tb14788.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mülsch A., Bassenge E., Busse R. Nitric oxide synthesis in endothelial cytosol: evidence for a calcium-dependent and a calcium-independent mechanism. Naunyn Schmiedebergs Arch Pharmacol. 1989 Dec;340(6 Pt 2):767–770. doi: 10.1007/BF00169688. [DOI] [PubMed] [Google Scholar]
  19. Pasyk E., Inazu M., Daniel E. E. CPA enhances Ca2+ entry in cultured bovine pulmonary arterial endothelial cells in an IP3-independent manner. Am J Physiol. 1995 Jan;268(1 Pt 2):H138–H146. doi: 10.1152/ajpheart.1995.268.1.H138. [DOI] [PubMed] [Google Scholar]
  20. Randriamampita C., Tsien R. Y. Emptying of intracellular Ca2+ stores releases a novel small messenger that stimulates Ca2+ influx. Nature. 1993 Aug 26;364(6440):809–814. doi: 10.1038/364809a0. [DOI] [PubMed] [Google Scholar]
  21. Schilling W. P., Cabello O. A., Rajan L. Depletion of the inositol 1,4,5-trisphosphate-sensitive intracellular Ca2+ store in vascular endothelial cells activates the agonist-sensitive Ca(2+)-influx pathway. Biochem J. 1992 Jun 1;284(Pt 2):521–530. doi: 10.1042/bj2840521. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Schilling W. P., Rajan L., Strobl-Jager E. Characterization of the bradykinin-stimulated calcium influx pathway of cultured vascular endothelial cells. Saturability, selectivity, and kinetics. J Biol Chem. 1989 Aug 5;264(22):12838–12848. [PubMed] [Google Scholar]
  23. Schilling W. P., Ritchie A. K., Navarro L. T., Eskin S. G. Bradykinin-stimulated calcium influx in cultured bovine aortic endothelial cells. Am J Physiol. 1988 Aug;255(2 Pt 2):H219–H227. doi: 10.1152/ajpheart.1988.255.2.H219. [DOI] [PubMed] [Google Scholar]
  24. Schmidt K., Mayer B., Kukovetz W. R. Effect of calcium on endothelium-derived relaxing factor formation and cGMP levels in endothelial cells. Eur J Pharmacol. 1989 Nov 7;170(3):157–166. doi: 10.1016/0014-2999(89)90536-0. [DOI] [PubMed] [Google Scholar]
  25. Schwarz G., Droogmans G., Nilius B. Multiple effects of SK&F 96365 on ionic currents and intracellular calcium in human endothelial cells. Cell Calcium. 1994 Jan;15(1):45–54. doi: 10.1016/0143-4160(94)90103-1. [DOI] [PubMed] [Google Scholar]
  26. Seidler N. W., Jona I., Vegh M., Martonosi A. Cyclopiazonic acid is a specific inhibitor of the Ca2+-ATPase of sarcoplasmic reticulum. J Biol Chem. 1989 Oct 25;264(30):17816–17823. [PubMed] [Google Scholar]
  27. Takemura H., Hughes A. R., Thastrup O., Putney J. W., Jr Activation of calcium entry by the tumor promoter thapsigargin in parotid acinar cells. Evidence that an intracellular calcium pool and not an inositol phosphate regulates calcium fluxes at the plasma membrane. J Biol Chem. 1989 Jul 25;264(21):12266–12271. [PubMed] [Google Scholar]
  28. Thastrup O., Cullen P. J., Drøbak B. K., Hanley M. R., Dawson A. P. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2466–2470. doi: 10.1073/pnas.87.7.2466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Thastrup O. Role of Ca2(+)-ATPases in regulation of cellular Ca2+ signalling, as studied with the selective microsomal Ca2(+)-ATPase inhibitor, thapsigargin. Agents Actions. 1990 Jan;29(1-2):8–15. doi: 10.1007/BF01964706. [DOI] [PubMed] [Google Scholar]
  30. Weber C., Kruse H. J., Sellmayer A., Erl W., Weber P. C. Platelet activating factor enhances receptor-operated Ca(++)-influx and subsequent prostacyclin synthesis in human endothelial cells. Biochem Biophys Res Commun. 1993 Sep 15;195(2):874–880. doi: 10.1006/bbrc.1993.2126. [DOI] [PubMed] [Google Scholar]
  31. Zheng X. F., Kwan C. Y., Daniel E. E. Role of intracellular Ca2+ in EDRF release in rat aorta. J Vasc Res. 1994 Jan-Feb;31(1):18–24. doi: 10.1159/000159027. [DOI] [PubMed] [Google Scholar]

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

RESOURCES