title: Interrelationships between PGE1 and PGI2 binding and stimulation of adenylate cyclase.
abstract: The effects of prostaglandin E1 (PGE1) and prostacyclin (PGI2) on hepatic adenylate cyclase were studied in plasma membranes isolated from Sprague-Dawley rat livers. Both PGE1 and PGI2 stimulated this enzyme complex to the same maximal levels and with approximately the same EC50 (10(-7) M). Maximally stimulating concentrations of PGE1 and PGI2 were examined alone and together; their effects were not additive, indicating that the same enzyme complex was shared. Although a receptor for PGE1 could be demonstrated with a dissociation constant of 1 X 10(-8) M, PGI2 was only 1/100 as effective in competing for PGE1 binding sites (KD, 1 X 10(-6) M), indicating that these two prostaglandins may act via separate membrane receptors. PGI2 is known to be unstable at neutral pH; however, we have determined its half-life during these assays by a sensitive bioassay and concluded that the degradation of PGI2 is not sufficient to account for its inability to dissociate [3H]PGE1 binding. Further evidence that PGI2 might act through a distinct receptor was found in animals whose PGE1 receptors were 40% downregulated with a corresponding 28% decrease in PGE1-sensitive adenylate cyclase activity. These membranes had no such decrease in PGI2-sensitive adenylate cyclase activity. We conclude that 1) hepatic adenylate cyclase is equally sensitive to PGE1 and PGI2; 2) the same adenylate cyclase complex responds to both prostaglandins; and 3) PGE1 and PGI2 interact with separate membrane receptors in rat liver.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000527:Alprostadil; D000818:Animals; D002460:Cell Line / Q000378:metabolism; D015232:Dinoprostone; D004789:Enzyme Activation; D011464:Epoprostenol / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D018078:Receptors, Prostaglandin E
chemical_list: D011453:Prostaglandins; D011458:Prostaglandins E; D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D011464:Epoprostenol; D000262:Adenylyl Cyclases; D000527:Alprostadil; D015232:Dinoprostone