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

    Research output: Contribution to journalArticlepeer-review

    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 (α and γ), Ca2+-independent PKCs (δ and ε), and the atypical isoform (ζ). PKCβ could not be detected, whereas PKCγ is likely to be of neural origin. All isoforms exhibited different distributions: PKCα, PKCε, and PKCζ were found in both particulate and soluble fractions. In contrast, PKCδ was mainly in the particulate fraction, and PKCγ was in the soluble fraction. Phorbol esters, which activate PKC and cause smooth muscle contraction, downregulated only the α and δ 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 4α- and 4β-phorbol ester pretreatment. Maximal tension in response to this agonist was not affected. We conclude that PKCα and/or PKCδ 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.
    Original languageEnglish
    Pages (from-to)806-812
    Number of pages6
    JournalCirculation research
    Volume78
    Issue number5
    Publication statusPublished - May 1996

    Keywords

    • Contraction
    • Phorbol ester
    • Protein kinase C
    • Small arteries
    • Vascular smooth muscle

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