Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1994 Jan;111(1):311–317. doi: 10.1111/j.1476-5381.1994.tb14061.x

Effect of a peptide inhibitor of protein kinase C on G-protein-mediated increase in myofilament Ca(2+)-sensitivity in rabbit arterial skinned muscle.

T Itoh 1, A Suzuki 1, Y Watanabe 1
PMCID: PMC1910052  PMID: 8012712

Abstract

1. To investigate the role of protein kinase C in the increase mediated by guanosine 5'-triphosphate (GTP)-binding proteins (G-proteins) in the sensitivity of the contractile proteins to Ca2+ in vascular smooth muscle, the effect of a novel peptide inhibitor of protein kinase C (PKC19-36) on Ca(2+)-induced contraction and myosin light chain (MLC) phosphorylation was studied in the presence and absence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) in beta-escin-skinned smooth muscle strips of rabbit mesenteric artery. For comparison, the effects were also observed of PKC19-36 on the action of phorbol 12,13-dibutylate (PDBu, an activator of PKC) on the two Ca(2+)-induced responses. 2. In beta-escin-skinned strips treated with ionomycin, Ca2+ (0.1-3 microM) concentration-dependently produced contraction in parallel with an increase in MLC-phosphorylation. GTP gamma S (10 microM) and PDBu (0.1 microM) each shifted both the Ca(2+)-force and Ca(2+)-MLC-phosphorylation relationships to the left without a significant change in either maximum response. The relationship between force and MLC-phosphorylation was not modified by either GTP gamma S or PDBu, indicating that the sensitivity of MLC-phosphorylation to Ca2+ is enhanced by both GTP gamma S and PDBu. 3. PKC19-36 itself modified neither the contraction nor MLC-phosphorylation induced by Ca2+ but it did block the PDBu-induced enhancement of these two Ca(2+)-induced responses. By contrast, PKC19-36 did not modify the GTP gamma S-induced enhancement of the two Ca(2+)-induced responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
311

Selected References

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

  1. Bourne H. R., Sanders D. A., McCormick F. The GTPase superfamily: a conserved switch for diverse cell functions. Nature. 1990 Nov 8;348(6297):125–132. doi: 10.1038/348125a0. [DOI] [PubMed] [Google Scholar]
  2. Chatterjee M., Tejada M. Phorbol ester-induced contraction in chemically skinned vascular smooth muscle. Am J Physiol. 1986 Sep;251(3 Pt 1):C356–C361. doi: 10.1152/ajpcell.1986.251.3.C356. [DOI] [PubMed] [Google Scholar]
  3. Cockcroft S., Gomperts B. D. Role of guanine nucleotide binding protein in the activation of polyphosphoinositide phosphodiesterase. Nature. 1985 Apr 11;314(6011):534–536. doi: 10.1038/314534a0. [DOI] [PubMed] [Google Scholar]
  4. Edelman A. M., Blumenthal D. K., Krebs E. G. Protein serine/threonine kinases. Annu Rev Biochem. 1987;56:567–613. doi: 10.1146/annurev.bi.56.070187.003031. [DOI] [PubMed] [Google Scholar]
  5. Fujiwara T., Itoh T., Kubota Y., Kuriyama H. Actions of a phorbol ester on factors regulating contraction in rabbit mesenteric artery. Circ Res. 1988 Nov;63(5):893–902. doi: 10.1161/01.res.63.5.893. [DOI] [PubMed] [Google Scholar]
  6. Fujiwara T., Itoh T., Kubota Y., Kuriyama H. Effects of guanosine nucleotides on skinned smooth muscle tissue of the rabbit mesenteric artery. J Physiol. 1989 Jan;408:535–547. doi: 10.1113/jphysiol.1989.sp017474. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gong M. C., Fuglsang A., Alessi D., Kobayashi S., Cohen P., Somlyo A. V., Somlyo A. P. Arachidonic acid inhibits myosin light chain phosphatase and sensitizes smooth muscle to calcium. J Biol Chem. 1992 Oct 25;267(30):21492–21498. [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 K., Kikuchi A., Sasaki T., Kuroda S., Kaibuchi K., Matsuura Y., Seki H., Saida K., Takai Y. Involvement of rho p21 in the GTP-enhanced calcium ion sensitivity of smooth muscle contraction. J Biol Chem. 1992 May 5;267(13):8719–8722. [PubMed] [Google Scholar]
  10. Hori M., Sato K., Sakata K., Ozaki H., Takano-Ohmuro H., Tsuchiya T., Sugi H., Kato I., Karaki H. Receptor agonists induce myosin phosphorylation-dependent and phosphorylation-independent contractions in vascular smooth muscle. J Pharmacol Exp Ther. 1992 May;261(2):506–512. [PubMed] [Google Scholar]
  11. House C., Kemp B. E. Protein kinase C contains a pseudosubstrate prototope in its regulatory domain. Science. 1987 Dec 18;238(4834):1726–1728. doi: 10.1126/science.3686012. [DOI] [PubMed] [Google Scholar]
  12. Ikebe M., Inagaki M., Kanamaru K., Hidaka H. Phosphorylation of smooth muscle myosin light chain kinase by Ca2+-activated, phospholipid-dependent protein kinase. J Biol Chem. 1985 Apr 25;260(8):4547–4550. [PubMed] [Google Scholar]
  13. Itoh T., Ikebe M., Kargacin G. J., Hartshorne D. J., Kemp B. E., Fay F. S. Effects of modulators of myosin light-chain kinase activity in single smooth muscle cells. Nature. 1989 Mar 9;338(6211):164–167. doi: 10.1038/338164a0. [DOI] [PubMed] [Google Scholar]
  14. Itoh T., Kajikuri J., Kuriyama H. Characteristic features of noradrenaline-induced Ca2+ mobilization and tension in arterial smooth muscle of the rabbit. J Physiol. 1992 Nov;457:297–314. doi: 10.1113/jphysiol.1992.sp019379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Itoh T., Kanmura Y., Kuriyama H., Sumimoto K. A phorbol ester has dual actions on the mechanical response in the rabbit mesenteric and porcine coronary arteries. J Physiol. 1986 Jun;375:515–534. doi: 10.1113/jphysiol.1986.sp016131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kitazawa T., Gaylinn B. D., Denney G. H., Somlyo A. P. G-protein-mediated Ca2+ sensitization of smooth muscle contraction through myosin light chain phosphorylation. J Biol Chem. 1991 Jan 25;266(3):1708–1715. [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Kubota Y., Nomura M., Kamm K. E., Mumby M. C., Stull J. T. GTP gamma S-dependent regulation of smooth muscle contractile elements. Am J Physiol. 1992 Feb;262(2 Pt 1):C405–C410. doi: 10.1152/ajpcell.1992.262.2.C405. [DOI] [PubMed] [Google Scholar]
  21. Morgan J. P., Morgan K. G. Stimulus-specific patterns of intracellular calcium levels in smooth muscle of ferret portal vein. J Physiol. 1984 Jun;351:155–167. doi: 10.1113/jphysiol.1984.sp015239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Nakamura F., Mino T., Yamamoto J., Naka M., Tanaka T. Identification of the regulatory site in smooth muscle calponin that is phosphorylated by protein kinase C. J Biol Chem. 1993 Mar 25;268(9):6194–6201. [PubMed] [Google Scholar]
  23. Nishikawa M., Sellers J. R., Adelstein R. S., Hidaka H. Protein kinase C modulates in vitro phosphorylation of the smooth muscle heavy meromyosin by myosin light chain kinase. J Biol Chem. 1984 Jul 25;259(14):8808–8814. [PubMed] [Google Scholar]
  24. Nishimura J., Kolber M., van Breemen C. Norepinephrine and GTP-gamma-S increase myofilament Ca2+ sensitivity in alpha-toxin permeabilized arterial smooth muscle. Biochem Biophys Res Commun. 1988 Dec 15;157(2):677–683. doi: 10.1016/s0006-291x(88)80303-6. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Persechini A., Kamm K. E., Stull J. T. Different phosphorylated forms of myosin in contracting tracheal smooth muscle. J Biol Chem. 1986 May 15;261(14):6293–6299. [PubMed] [Google Scholar]
  27. Rembold C. M. Modulation of the [Ca2+] sensitivity of myosin phosphorylation in intact swine arterial smooth muscle. J Physiol. 1990 Oct;429:77–94. doi: 10.1113/jphysiol.1990.sp018245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sasaguri T., Hirata M., Kuriyama H. Dependence on Ca2+ of the activities of phosphatidylinositol 4,5-bisphosphate phosphodiesterase and inositol 1,4,5-trisphosphate phosphatase in smooth muscles of the porcine coronary artery. Biochem J. 1985 Nov 1;231(3):497–503. doi: 10.1042/bj2310497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sutton T. A., Haeberle J. R. Phosphorylation by protein kinase C of the 20,000-dalton light chain of myosin in intact and chemically skinned vascular smooth muscle. J Biol Chem. 1990 Feb 15;265(5):2749–2754. [PubMed] [Google Scholar]

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

RESOURCES