Selective inactivation by endogenous protein kinase C of human platelet high-affinity GTPase coupled with PAF receptors.
Incubation of human platelets with protein kinase C activator 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA) abolished stimulation of membrane high-affinity GTPase by platelet-activating factor (PAF). GTPase stimulation by epinephrine decreased by 30%, while the prostaglandin E1 (PGE1) effect was unchanged. Basal GTPase activity (22.4 +/- 1.1 pmol Pi/min per mg protein) was not affected by PMA. Therefore, a study was performed of the effect of endogenous protein kinase C activation on adenylate cyclase regulation by agonists. PMA pretreatment completely suppressed PAF inhibition of basal adenylate cyclase activity but hardly influenced the inhibition by PAF of forskolin-stimulated activity. Adenylate cyclase inhibition by epinephrine in the presence of propranolol was not suppressed completely after platelet incubation with PMA. Epinephrine effects on basal and forskolin-stimulated activities decreased equally. Platelet pretreatment with PMA increased PGE1-stimulated activity by abolishing the inhibitory effect of high GTP concentrations. These studies indicate that protein kinase C selectively inhibits PAF effects, presumably by inactivating a GTP-binding protein coupled with PAF receptors.
Avdonin
P V
PV
Institute of Experimental Cardiology, Academy of Medical Sciences, Moscow, USSR.
Svitina-Ulitina
I V
IV
Tkachuk
V A
VA
D000262:Adenylyl Cyclases / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors* / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors*; D010972:Platelet Activating Factor / Q000494:pharmacology; D010980:Platelet Membrane Glycoproteins; D011493:Protein Kinase C / Q000097:blood*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D005576:Colforsin; D011493:Protein Kinase C; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases; D000262:Adenylyl Cyclases; D013755:Tetradecanoylphorbol Acetate; D004837:Epinephrine