Evidence that phospholipid turnover is the signal transducing system coupled to serotonin-S2 receptor sites.
Upon stimulation with serotonin of washed human platelets prelabeled with [32P]orthophosphate, we found an approximately 250% increase in [32P]phosphatidic acid (PA) formation, a small decrease in [32P]phosphatidylinositol 4,5-bisphosphate, and a concomitant increase in [32P]phosphatidylinositol 4-phosphate. Using [3H]arachidonate for prelabeling, [3H]diacylglycerol accumulated transiently at 10 s after addition of the agonist, [3H]PA increased but to a lower extent compared to 32P-labeled lipid, and the formation of both [3H]polyphosphoinositides increased. The serotonin-induced dose-dependent changes in [32P]PA correlate with its effect on the changes in slope of aggregation of platelets. The potency of 13 drugs to antagonize the serotonin-induced PA formation closely corresponds to both their potency to inhibit platelet aggregation and their binding affinity for serotonin-S2 receptor sites. It is suggested that at least part of the signal transducing system following activation of the serotonin-S2 receptors involves phospholipase C catalyzed inositol lipid breakdown yielding diacylglycerol which is subsequently phosphorylated to PA.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010710:Phosphates / Q000097:blood*; D010712:Phosphatidic Acids / Q000097:blood; D010716:Phosphatidylinositols / Q000097:blood; D010743:Phospholipids / Q000097:blood*; D010761:Phosphorus Radioisotopes; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000097:blood*; D014316:Tritium
D001095:Arachidonic Acids; D010710:Phosphates; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D010743:Phospholipids; D010761:Phosphorus Radioisotopes; D011985:Receptors, Serotonin; D014316:Tritium; D016718:Arachidonic Acid; D012701:Serotonin