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    The phorbol ester, TPA inhibits glucagon-stimulated adenylate cyclase activity.

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    Authors
    Heyworth, Clare M
    Whetton, Anthony D
    Kinsella, Anne R
    Houslay, M D
    Affiliation
    Department of Biochemistry and Applied Molecular Biology, University of Manchester Institute of Science and Technology, PO Box 88, Manchester M60 1QD
    Issue Date
    1984-05-07
    
    Metadata
    Show full item record
    Abstract
    The ability of glucagon (10 nM) to increase hepatocyte intracellular cyclic AMP concentrations was reduced markedly by the tumour-promoting phorbol ester TPA (12-O-tetradecanoyl phorbol-13-acetate). The half-maximal inhibitory effect occurred at 0.14 ng/ml TPA. This action occurred in the presence of the cyclic AMP phosphodiesterase inhibitor isobutylmethylxanthine (1 mM) indicating that TPA inhibited glucagon-stimulated adenylate cyclase activity. TPA did not affect either the binding of glucagon to its receptor or ATP concentrations within the cell. TPA did inhibit the increase in intracellular cyclic AMP initiated by the action of cholera toxin (1 microgram/ml) under conditions where phosphodiesterase activity was blocked. TPA did not inhibit glucagon-stimulated adenylate cyclase activity in a broken plasma membrane preparation unless Ca2+, phosphatidylserine and ATP were also present. It is suggested that TPA exerts its inhibitory effect on adenylate cyclase through the action of protein kinase C. This action is presumed to be exerted at the point of regulation of adenylate cyclase by guanine nucleotides.
    Citation
    The phorbol ester, TPA inhibits glucagon-stimulated adenylate cyclase activity. 1984, 170 (1):38-42 FEBS Lett.
    Journal
    FEBS Letters
    URI
    http://hdl.handle.net/10541/123697
    DOI
    10.1016/0014-5793(84)81364-2
    PubMed ID
    6327375
    Type
    Article
    Language
    en
    ISSN
    0014-5793
    ae974a485f413a2113503eed53cd6c53
    10.1016/0014-5793(84)81364-2
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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