Counteraction of calcium-activated, phospholipid-dependent protein kinase activation by adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in platelets.
In intact human platelets activated by thrombin, diacylglycerol is produced with the concomitant disappearance of phosphatidylinositol (PI). This reaction is associated with phosphorylation of a protein having a molecular weight of about 40,000 (40 K protein) and serotonin release. All the reactions are inhibited in a parallel manner by incubation of platelets with either dibutyryl cyclic AMP or 8-bromocyclic GMP, prior to the stimulation by thrombin. The inhibition of these reactions is inversely related to phosphorylation of another group of platelet proteins. Since Ca2+-activated, phospholipid-dependent protein kinase (C-Kinase) is activated by diacylglycerol and is responsible for 40 K protein phosphorylation (Kawahara, Y., Takai, Y., Minakuchi, R., Sano, K., & Nishizuka, Y. (1980) Biochem. Biophys. Res. Commun. 97, 309-317), the results suggest that in platelets both cyclic AMP and cyclic GMP may serve as inhibitors of C-Kinase by counteracting the receptor-linked PI breakdown probably through the actions of cyclic nucleotide-dependent protein kinases.
D000527:Alprostadil; D001792:Blood Platelets / Q000201:enzymology*; D003994:Bucladesine / Q000494:pharmacology*; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D010716:Phosphatidylinositols / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011458:Prostaglandins E / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology
D004075:Diglycerides; D010716:Phosphatidylinositols; D010750:Phosphoproteins; D011458:Prostaglandins E; D047428:Protein Kinase Inhibitors; C016276:8-bromocyclic GMP; D003994:Bucladesine; D011494:Protein Kinases; D013917:Thrombin; D000527:Alprostadil; D006152:Cyclic GMP