Activation of protein kinase C alters the interaction of α2‐adrenoceptors and the inhibitory GTP‐binding protein (Gi) in human platelets

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Abstract
The effect of 12-tetradecanoyl phorbol 13-acetate (TPA) on the hormonal modulation of adenylate cyclase was studied. The effect of epinephrine (α2-adrenergic action) was markedly diminished in membranes from TPA-treated platelets as compared to the controls. Interestingly, the inhibitory effect of guanylyl imido diphosphate (Gpp(NH)p) was not altered. Neither the number of α2-adrenoceptors nor their affinity for [3H]yohimbine were affected by the treatment with TPA. In control platelets, 77% of the receptors were in a high-affinity state for epinephrine and 22% in a low-affinity state; Gpp(NH)p shifted the receptor affinity towards the low-affinity conformation. In membranes from TPA-treated platelets, the receptors were in the low-affinity state and no further decrease in affinity was induced by Gpp(NH)p. Our data suggest that activation of protein kinase C in platelets blocks the hormonal inhibition of adenylate cyclase by interfering with the receptor-Gi interaction.