Cytoplasmic Ca2+ in platelets is controlled by cyclic AMP: antagonism between stimulators and inhibitors of adenylate cyclase.
Activation of platelets by thrombin rapidly increases cytoplasmic free calcium, [Ca2+]i, measured by Quin -2, and induces secretion. Stimulators of adenylate cyclase (i.e. PGI2, PGD2, forskolin) suppressed or reversed the increase of [Ca2+]i. Inhibitors of adenylate cyclase (i.e. epinephrine, ADP), added before or after thrombin, counteracted PGI2, PGD2 and forskolin and thereby increased [Ca2+]i and restored secretion. Responses to epinephrine (via alpha-2 adrenoreceptors) and ADP were independent of extracellular Ca2+, but required maintained occupancy of thrombin receptors and intact cAMP-phosphodiesterase activity. These results indicate that cAMP serves as an inhibitory second-messenger that antagonizes the mobilization of Ca2+, an activator second-messenger.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000502:physiology*; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D005576:Colforsin; D000242:Cyclic AMP / Q000502:physiology*; D004224:Diterpenes / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D015230:Prostaglandin D2; D011457:Prostaglandins D / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D004224:Diterpenes; D011457:Prostaglandins D; D005576:Colforsin; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D000242:Cyclic AMP; D013917:Thrombin; D000262:Adenylyl Cyclases; D015230:Prostaglandin D2; D002118:Calcium; D004837:Epinephrine