title: Evidence that cyclic AMP may regulate Ca2+-mobilization and phospholipases in thrombin-stimulated human platelets.
abstract: The regulation of human platelet responses by cyclic AMP (cAMP) has been investigated by measuring thrombin-stimulated serotonin release, Ca2+ uptake and phospholipase activity. Thrombin-induced 1,2-diacylglycerol (DG) formation as a result of phospholipase C activation was inhibited by pretreatment with dibutyryl cAMP (dbcAMP) in a dose-dependent manner. Subsequent failure to produce phosphatidic acid (PA), which is converted from 1,2-DG by phosphorylation and would serve as intracellular Ca2+ ionophore, appeared to parallel the decrease in Ca2+ uptake activity. Phospholipase A2 activity, monitored by the production of [3H]lysophosphatidylcholine and [3H]lysophosphatidylethanolamine, was also suppressed by dbcAMP. These data indicate that the intracellular cAMP level may be closely associated with Ca2+ uptake and phospholipases activation. In addition, it is suggested that alteration of intracellular cAMP regulates phospholipase activation and consequently platelet responses, perhaps by controlling available Ca2+ content.
mesh_terms: D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism*; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000097:blood*; D000242:Cyclic AMP / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D010740:Phospholipases / Q000097:blood*; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*
chemical_list: D012701:Serotonin; D003994:Bucladesine; D000242:Cyclic AMP; D010740:Phospholipases; D013917:Thrombin; D002118:Calcium