Abstract
Platelet activation is associated with the active metabolism of inositol phospholipids. The effects of cAMP and cGMP on thrombin-stimulated human platelet responses and membrane phospholipid metabolism were investigated. Thrombin (0.1U/ml)-induced aggregation and serotonin release were prevented by pretreatment with dibutyryl cyclic AMP (dbcAMP) in a dose-dependent manner. 1, 2-Diacylglycerol production as a result of phospholipase C activation and formation of lysophospholipids were also suppressed by addition of dbcAMP. Two opposite hypotheses (stimulation or inhibition) are still discussed about the role of cGMP in platelet function. 8-Bromo cyclic GMP (8bcGMP) partially inhibited aggregation and serotonin secretion stimulated by thrombin. Phospholipase C activity, monitored by phosphatidylinositol breakdown and phosphatidic acid formation, and arachidonic acid liberation were also diminished by 8bcGMP. Although the inhibitory effect of 8bcGMP on thrombin-stimulated platelet is less than that of the same dose of dbcAMP, 8bcGMP suppresses platelet responses. A plausible explanation for its inhibitory effect is that 8bcGMP may inhibit the receptor-linked breakdown of inositol phospholipids and arachidonate liberation.
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