Inhibition by cyclic AMP of guanine nucleotide‐induced activation of phosphoinositide‐specific phospholipase C in human platelets

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Abstract
Phosphoinositide‐specific phospholipase C (PLC) activity of human platelet membranes was activated by the nonhydrolyzable guanine nucleotide GTPγS. This activation did not occur in either membranes prepared from dibutyryl cyclic AMP‐pretreated platelets (A‐membranes) or those prepared from untreated cells and subsequently incubated with cyclic AMP (cAMP) (B‐membranes). This cAMP‐mediated inhibition was abolished in the presence of inhibitors of cAMP‐dependent protein kinase (A‐kinase), suggesting that the inhibition was due to phosphorylation of (a) protein component(s). No significant differences were observed in the basal PLC activity and the extent of pertussis toxin‐catalyzed ADP‐ribosylation among control membranes and the two types of phosphorylated membranes (A‐ and B‐membranes). GTP‐binding activities of Gs, Gi and GTP‐binding proteins of lower molecular masses were not altered by the phosphorylation of the membranes. These findings suggest that a GTP‐binding protein is involved in the GTPγS‐mediated activation of PLC and that cAMP (plus A‐kinase) inhibits this activation by phosphorylating a membrane protein (probably a 240‐kDa protein), rather than the GTP‐binding protein or PLC itself. It is likely that this phosphorylation uncouples the GTP‐binding protein from PLC.

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