POTENTIATION OF ADENYLYL-CYCLASE IN HUMAN PERIPHERAL-BLOOD MONONUCLEAR-CELLS BY CELL-ACTIVATING STIMULI

MWSM DOOPER, Y HOEKSTRA, JGR DEMONCHY, HF KAUFFMAN

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    Abstract

    The isoprenaline-induced production of cAMP in human peripheral blood mononuclear cells (PBMC) was potentiated significantly by incubating PBMC with isoprenaline in the presence of phytohaemagglutinin (PHA), Concanavalin A (Con A) or A23187. This potentiation, that proved to be dependent on the concentration of PHA, Con A or A23187, increased the maximal response but did not cause a change in the potency of isoprenaline. Potentiation could not be induced by the phorbol ester phorbolmyristate acetate, suggesting that protein kinase C-dependent pathways are not likely to be involved in potentiation of adenylyl cyclase. Potentiation could be inhibited by chelating extracellular Ca2+ with EGTA and also by N-(6-aminohexyl)-5-chloro-1-naphtalenesulfonamine, an inhibitor of calmodulin. Potentiation could not be induced by preincubation of PBMC with PHA, suggesting that transient biochemical changes are involved. It was concluded from these results that potentiation in PBMC probably involves the activation of Ca2+/calmodulin-dependent adenylyl cyclase subtypes. Potentiation of the adenylyl cyclase activity could be an important physiological mechanism in vivo preventing cells from becoming ''over stimulated''.

    Original languageEnglish
    Pages (from-to)289-294
    Number of pages6
    JournalBiochemical Pharmacology
    Volume47
    Issue number2
    Publication statusPublished - 20-Jan-1994

    Keywords

    • PROTEIN-KINASE-C
    • CYCLIC-AMP ACCUMULATION
    • INOSITOL PHOSPHATE GENERATION
    • PHORBOL-MYRISTATE ACETATE
    • HUMAN ASTROCYTOMA-CELLS
    • SIGNAL TRANSDUCTION
    • T-CELLS
    • ADENOSINE-MONOPHOSPHATE
    • CHEMOTACTIC-PEPTIDE
    • RECEPTOR COMPLEX

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