January 1, 1982
View Full PaperCounteraction of Calcium-Activated, Phospholipid-Dependent Protein Kinase Activation by Adenosine 3′,5′-Monophosphate and Guanosine 3′,5′-Monophosphate in Platelets1
Key Result
Incubation of human platelets with dibutyryl cyclic AMP or 8-bromocyclic GMP inhibited thrombin-induced diacylglycerol production, 40 K protein phosphorylation, and serotonin release.
Structured PICO
P
Population
Intact human platelets
I
Intervention
Incubation with either dibutyryl cyclic AMP or 8-bromocyclic GMP prior to stimulation by thrombin
C
Comparator
Thrombin stimulation without prior incubation
O
Outcome
Inhibition of diacylglycerol production, phosphatidylinositol disappearance, 40 K protein phosphorylation, and serotonin releasesurrogate
Cyclic AMP and cyclic GMP counteract receptor-linked phosphatidylinositol breakdown, suggesting they serve as inhibitors of C-Kinase in platelets.
Abstract
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.