Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Oct;107(2):282–287. doi: 10.1111/j.1476-5381.1992.tb12739.x

Participation of protein kinase C in endothelin-1-induced contraction in rat aorta: studies with a new tool, calphostin C.

H Shimamoto 1, Y Shimamoto 1, C Y Kwan 1, E E Daniel 1
PMCID: PMC1907897  PMID: 1384908

Abstract

1. Calphostin C at 10(-6) M was shown to be selective and highly effective in inhibiting contractile responses of rat aortae to 12-o-tetradecanoylphorbol-13-acetate, while it had no effect on contractile responses to elevated KCl. 2. In the rat aorta, endothelin-1 (ET-1) developed a sustained tonic contraction dose-dependently in both normal Ca(2+)-containing Krebs and Ca(2+)-free Krebs containing 1 mM EGTA. Calphostin C (10(-6) M), a selective protein kinase C inhibitor, antagonized the maximal tensions for cumulative addition of 10(-8) M ET-1 by 13.2% in Ca(2+)-containing medium and 25.8% in Ca(2+)-free Krebs containing 1 mM EGTA. 3. In both Ca(2+)-containing medium and Ca(2+)-free Krebs containing 1 mM EGTA, precontraction with 10(-8) M ET-1 had no effects on the contractile response to subsequently added 10(-6) M 12-o-tetradecanoylphorbol-13-acetate (TPA), an activator of protein kinase C. 4. In Ca(2+)-free Krebs containing 1 mM EGTA, precontraction with 10(-6) M TPA potentiated the contractile response to subsequently added 10(-8) M ET-1, whereas this potentiation was abolished by pretreatment with 10(-6) M calphostin C. The mechanism of the TPA-induced potentiating effect remains to be determined. 5. These results suggest that the participation of protein kinase C in the 10(-8) M ET-1-induced contraction may be 13.2% and 25.8% in the presence and absence of extracellular Ca2+, respectively, and that mechanisms other than protein kinase C may be predominantly responsible for ET-1-induced tonic contraction.

Full text

PDF
282

Selected References

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

  1. Abdel-Latif A. A. Calcium-mobilizing receptors, polyphosphoinositides, and the generation of second messengers. Pharmacol Rev. 1986 Sep;38(3):227–272. [PubMed] [Google Scholar]
  2. Bolger G. T., Liard F., Jaramillo J. Tissue selectivity and calcium dependence of contractile responses to endothelin. J Cardiovasc Pharmacol. 1990 Jun;15(6):946–958. doi: 10.1097/00005344-199006000-00013. [DOI] [PubMed] [Google Scholar]
  3. Chabrier P. E., Auguet M., Roubert P., Lonchampt M. O., Gillard V., Guillon J. M., Delaflotte S., Braquet P. Vascular mechanism of action of endothelin-1: effect of Ca2+ antagonists. J Cardiovasc Pharmacol. 1989;13 (Suppl 5):S32–S45. doi: 10.1097/00005344-198900135-00009. [DOI] [PubMed] [Google Scholar]
  4. Deng L. Y., Schiffrin E. L. Calcium dependence of effects of endothelin on rat mesenteric microvessels. Can J Physiol Pharmacol. 1991 Jun;69(6):798–804. doi: 10.1139/y91-120. [DOI] [PubMed] [Google Scholar]
  5. Drenth J. P., Nishimura J., Nouailhetas V. L., van Breemen C. Receptor-mediated C-kinase activation contributes to alpha-adrenergic tone in rat mesenteric resistance artery. J Hypertens Suppl. 1989 Sep;7(4):S41–S45. [PubMed] [Google Scholar]
  6. Guan Y. Y., Kwan C. Y., Daniel E. E. The effects of EGTA on vascular smooth muscle contractility in calcium-free medium. Can J Physiol Pharmacol. 1988 Aug;66(8):1053–1056. doi: 10.1139/y88-172. [DOI] [PubMed] [Google Scholar]
  7. Haller H., Smallwood J. I., Rasmussen H. Protein kinase C translocation in intact vascular smooth muscle strips. Biochem J. 1990 Sep 1;270(2):375–381. doi: 10.1042/bj2700375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hidaka H., Inagaki M., Kawamoto S., Sasaki Y. Isoquinolinesulfonamides, novel and potent inhibitors of cyclic nucleotide dependent protein kinase and protein kinase C. Biochemistry. 1984 Oct 9;23(21):5036–5041. doi: 10.1021/bi00316a032. [DOI] [PubMed] [Google Scholar]
  9. Hirata Y., Yoshimi H., Takata S., Watanabe T. X., Kumagai S., Nakajima K., Sakakibara S. Cellular mechanism of action by a novel vasoconstrictor endothelin in cultured rat vascular smooth muscle cells. Biochem Biophys Res Commun. 1988 Aug 15;154(3):868–875. doi: 10.1016/0006-291x(88)90220-3. [DOI] [PubMed] [Google Scholar]
  10. Itoh H., Higuchi H., Hiraoka N., Ito M., Konishi T., Nakano T., Lederis K. Contraction of rat thoracic aorta strips by endothelin-1 in the absence of extracellular Ca2+. Br J Pharmacol. 1991 Dec;104(4):847–852. doi: 10.1111/j.1476-5381.1991.tb12516.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Jiang M. J., Morgan K. G. Intracellular calcium levels in phorbol ester-induced contractions of vascular muscle. Am J Physiol. 1987 Dec;253(6 Pt 2):H1365–H1371. doi: 10.1152/ajpheart.1987.253.6.H1365. [DOI] [PubMed] [Google Scholar]
  12. Kobayashi E., Ando K., Nakano H., Iida T., Ohno H., Morimoto M., Tamaoki T. Calphostins (UCN-1028), novel and specific inhibitors of protein kinase C. I. Fermentation, isolation, physico-chemical properties and biological activities. J Antibiot (Tokyo) 1989 Oct;42(10):1470–1474. doi: 10.7164/antibiotics.42.1470. [DOI] [PubMed] [Google Scholar]
  13. Kobayashi E., Nakano H., Morimoto M., Tamaoki T. Calphostin C (UCN-1028C), a novel microbial compound, is a highly potent and specific inhibitor of protein kinase C. Biochem Biophys Res Commun. 1989 Mar 15;159(2):548–553. doi: 10.1016/0006-291x(89)90028-4. [DOI] [PubMed] [Google Scholar]
  14. Kodama M., Kanaide H., Abe S., Hirano K., Kai H., Nakamura M. Endothelin-induced Ca-independent contraction of the porcine coronary artery. Biochem Biophys Res Commun. 1989 May 15;160(3):1302–1308. doi: 10.1016/s0006-291x(89)80145-7. [DOI] [PubMed] [Google Scholar]
  15. Komuro I., Kurihara H., Sugiyama T., Yoshizumi M., Takaku F., Yazaki Y. Endothelin stimulates c-fos and c-myc expression and proliferation of vascular smooth muscle cells. FEBS Lett. 1988 Oct 10;238(2):249–252. doi: 10.1016/0014-5793(88)80489-7. [DOI] [PubMed] [Google Scholar]
  16. Marsden P. A., Danthuluri N. R., Brenner B. M., Ballermann B. J., Brock T. A. Endothelin action on vascular smooth muscle involves inositol trisphosphate and calcium mobilization. Biochem Biophys Res Commun. 1989 Jan 16;158(1):86–93. doi: 10.1016/s0006-291x(89)80180-9. [DOI] [PubMed] [Google Scholar]
  17. Miasiro N., Yamamoto H., Kanaide H., Nakamura M. Does endothelin mobilize calcium from intracellular store sites in rat aortic vascular smooth muscle cells in primary culture? Biochem Biophys Res Commun. 1988 Oct 14;156(1):312–317. doi: 10.1016/s0006-291x(88)80841-6. [DOI] [PubMed] [Google Scholar]
  18. Mori T., Yanagisawa T., Taira N. Phorbol 12,13-dibutyrate increases vascular tone but has a dual action on intracellular calcium levels in porcine coronary arteries. Naunyn Schmiedebergs Arch Pharmacol. 1990 Mar;341(3):251–255. doi: 10.1007/BF00169739. [DOI] [PubMed] [Google Scholar]
  19. Murakawa K., Kohno M., Yokokawa K., Yasunari K., Horio T., Kurihara N., Takeda T. Endothelin-induced renal vasoconstriction and increase in cytosolic calcium in renal vascular smooth muscle cells. Clin Exp Hypertens A. 1990;12(6):1037–1048. doi: 10.3109/10641969009073516. [DOI] [PubMed] [Google Scholar]
  20. Nakadate T., Jeng A. Y., Blumberg P. M. Comparison of protein kinase C functional assays to clarify mechanisms of inhibitor action. Biochem Pharmacol. 1988 Apr 15;37(8):1541–1545. doi: 10.1016/0006-2952(88)90016-0. [DOI] [PubMed] [Google Scholar]
  21. Nishimura J., Khalil R. A., Drenth J. P., van Breemen C. Evidence for increased myofilament Ca2+ sensitivity in norepinephrine-activated vascular smooth muscle. Am J Physiol. 1990 Jul;259(1 Pt 2):H2–H8. doi: 10.1152/ajpheart.1990.259.1.H2. [DOI] [PubMed] [Google Scholar]
  22. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  23. Ohlstein E. H., Horohonich S., Hay D. W. Cellular mechanisms of endothelin in rabbit aorta. J Pharmacol Exp Ther. 1989 Aug;250(2):548–555. [PubMed] [Google Scholar]
  24. Omura S., Iwai Y., Hirano A., Nakagawa A., Awaya J., Tsuchya H., Takahashi Y., Masuma R. A new alkaloid AM-2282 OF Streptomyces origin. Taxonomy, fermentation, isolation and preliminary characterization. J Antibiot (Tokyo) 1977 Apr;30(4):275–282. doi: 10.7164/antibiotics.30.275. [DOI] [PubMed] [Google Scholar]
  25. Rasmussen H., Takuwa Y., Park S. Protein kinase C in the regulation of smooth muscle contraction. FASEB J. 1987 Sep;1(3):177–185. [PubMed] [Google Scholar]
  26. Resink T. J., Scott-Burden T., Bühler F. R. Endothelin stimulates phospholipase C in cultured vascular smooth muscle cells. Biochem Biophys Res Commun. 1988 Dec 30;157(3):1360–1368. doi: 10.1016/s0006-291x(88)81025-8. [DOI] [PubMed] [Google Scholar]
  27. Rüegg U. T., Burgess G. M. Staurosporine, K-252 and UCN-01: potent but nonspecific inhibitors of protein kinases. Trends Pharmacol Sci. 1989 Jun;10(6):218–220. doi: 10.1016/0165-6147(89)90263-0. [DOI] [PubMed] [Google Scholar]
  28. Sugiura M., Inagami T., Hare G. M., Johns J. A. Endothelin action: Inhibition by a protein kinase C inhibitor and involvement of phosphoinositols. Biochem Biophys Res Commun. 1989 Jan 16;158(1):170–176. doi: 10.1016/s0006-291x(89)80193-7. [DOI] [PubMed] [Google Scholar]
  29. Takuwa Y., Kelley G., Takuwa N., Rasmussen H. Protein phosphorylation changes in bovine carotid artery smooth muscle during contraction and relaxation. Mol Cell Endocrinol. 1988 Nov;60(1):71–86. doi: 10.1016/0303-7207(88)90121-9. [DOI] [PubMed] [Google Scholar]
  30. Tamaoki T., Nomoto H., Takahashi I., Kato Y., Morimoto M., Tomita F. Staurosporine, a potent inhibitor of phospholipid/Ca++dependent protein kinase. Biochem Biophys Res Commun. 1986 Mar 13;135(2):397–402. doi: 10.1016/0006-291x(86)90008-2. [DOI] [PubMed] [Google Scholar]
  31. Yanagisawa M., Kurihara H., Kimura S., Tomobe Y., Kobayashi M., Mitsui Y., Yazaki Y., Goto K., Masaki T. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature. 1988 Mar 31;332(6163):411–415. doi: 10.1038/332411a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES