title: Activation of protein kinase C alters the interaction of alpha 2-adrenoceptors and the inhibitory GTP-binding protein (Gi) in human platelets.
abstract: The effect of 12-tetradecanoyl phorbol 13-acetate (TPA) on the hormonal modulation of adenylate cyclase was studied. The effect of epinephrine (alpha 2-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 alpha 2-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.
authors.affiliation: Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, México DF.
authors.forename: J A
authors.initials: JA
authors.lastname: García-Sáinz
authors.forename: G
authors.initials: G
authors.lastname: Gutiérrez-Venegas
mesh_terms: D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000097:blood*; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D011493:Protein Kinase C / Q000097:blood*; D011942:Receptors, Adrenergic, alpha / Q000097:blood*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015016:Yohimbine / Q000378:metabolism
chemical_list: D011942:Receptors, Adrenergic, alpha; D005576:Colforsin; D015016:Yohimbine; D006165:Guanylyl Imidodiphosphate; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; D013755:Tetradecanoylphorbol Acetate; D004837:Epinephrine