Human platelet secretion and aggregation induced by calcium ionophores. Inhibition by PGE1 and dibutyryl cyclic AMP.
Ca2+, Mg2+-ionophores X537A and A23,187 (10(-7)-10(-6) M) induced the release of adenine nucleotides adenosine diphosphate (ADP, adenosine triphosphate (ATP), serotonin, beta-glucuronidase, Ca2+, and Mg2+ from washed human platelets. Enzymes present in the cytoplasm or mitochondria, and Zn2+ were not released. The rate of ATP and Ca2+ release measured by firefly lantern extract and murexide dye, respectively, was equivalent to that produced by the physiological stimulant thrombin. Ionophore-induced release of ADP, and serotonin was substantially (approximately 60%) but not completely inhibited by EGTA, EDTA, and high extracellular Mg2+, without significant reduction of Ca2+ release. The ionophore-induced release reaction is therefore partly dependent upon uptake of extracellular Ca2+ (demonstrated using 45Ca), but also occurs to a significant extent due to release into the cytoplasm of intracellular Ca2+. The ionophore-induced release reaction and aggregation of platelets could be blocked by prostaglandin E1 (PGE1) or dibutyryl cyclic AMP. The effects of PGE1, and N6, O2-dibutyryl adenosine 3':5'-cyclic monophosphoric acid (dibutyryl cAMP) were synergistically potentiated by the phosphodiesterase inhibitor theophylline. It is proposed that Ca2+ is the physiological trigger for platelet secretion and aggregation and that its intracellular effects are strongly modulated by adenosine 3':5'-cyclic monophosphoric acid (cyclic AMP).
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D003994:Bucladesine / Q000494:pharmacology*; D000001:Calcimycin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D004492:Edetic Acid / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D007832:Lasalocid / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011458:Prostaglandins E / Q000494:pharmacology*; D012701:Serotonin / Q000378:metabolism; D013806:Theophylline / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D015032:Zinc / Q000378:metabolism
D000900:Anti-Bacterial Agents; D011458:Prostaglandins E; D012701:Serotonin; D000001:Calcimycin; D004533:Egtazic Acid; D000244:Adenosine Diphosphate; D003994:Bucladesine; D000255:Adenosine Triphosphate; D004492:Edetic Acid; D013806:Theophylline; D005966:Glucuronidase; D013917:Thrombin; D008274:Magnesium; D015032:Zinc; D002118:Calcium; D007832:Lasalocid