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(Circulation Research. 1996;78:806-812.)
© 1996 American Heart Association, Inc.

Articles

Identification of Protein Kinase C Isoforms in Rat Mesenteric Small Arteries and Their Possible Role in Agonist-Induced Contraction

Vasken Ohanian, Jacqueline Ohanian, Linda Shaw, Sylvia Scarth, Peter J. Parker, Anthony M. Heagerty

From the Department of Medicine (V.O., J.O., L.S., S.S., A.M.H.), Manchester (UK) Royal Infirmary, and the Protein Phosphorylation Laboratory (P.J.P.), Imperial Cancer Research Fund, London, UK.

Correspondence to Dr V. Ohanian, Department of Medicine, Manchester Royal Infirmary, Oxford Road, Manchester M13 9WL, England.

Abstract We have identified immunologically the protein kinase C (PKC) isoforms present in rat mesenteric small arteries, defined their distribution between particulate and soluble fractions, and studied their involvement in phorbol ester–induced contraction. Our analysis revealed the presence of the Ca²⁺-dependent PKCs ( and ), Ca²⁺-independent PKCs ( and ), and the atypical isoform (). PKCß could not be detected, whereas PKC is likely to be of neural origin. All isoforms exhibited different distributions: PKC, PKC, and PKC were found in both particulate and soluble fractions. In contrast, PKC was mainly in the particulate fraction, and PKC was in the soluble fraction. Phorbol esters, which activate PKC and cause smooth muscle contraction, downregulated only the and isoforms. This was associated with a parallel loss of contractile response to phorbol ester. The force developed to submaximal concentrations of noradrenaline was decreased after phorbol dibutyrate pretreatment, although the sensitivity and maximal response were unchanged. Phorbol ester pretreatment did not affect the contractile response to vasopressin. The sensitivity to non–receptor-mediated contraction, caused by K⁺ in the presence of prazosin, was slightly reduced by 4- and 4ß-phorbol ester pretreatment. Maximal tension in response to this agonist was not affected. We conclude that PKC and/or PKC is necessary for phorbol ester–mediated contraction but is not essential for noradrenaline-, vasopressin-, or K⁺-induced contraction, demonstrating differences in the mechanisms involved in the contractile response between these agents.

Key Words: protein kinase C • phorbol ester • contraction • small arteries • vascular smooth muscle

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