Beta 2-adrenergic regulation of prostaglandin D2 receptor in rabbit platelets.
[3H]Prostaglandin D2 binding to rabbit platelets was increased by about 150% in the presence of beta-adrenoceptor agonist, isoproterenol. The isoproterenol-induced potentiation of the [3H]prostaglandin D2 binding gave a bell-shaped dose-response relationship (maximum response at 3 X 10(-8) M) in a stereospecific manner. Similar and moderate potentiation was obtained with terbutaline. On the other hand, beta-adrenoceptor antagonists such as alprenolol, propranolol and butoxamine (beta 2-specific) had no potentiating effect on [3H]prostaglandin D2 binding; rather, they abolished the isoproterenol-induced increase of [3H]prostaglandin D2 binding. The beta 1-specific antagonist, metoprolol, did not have any effect. Rabbit platelets were found to possess one [3H]prostaglandin D2 binding site (Kd = 6 X 10(-7) M, Bmax = 787 fmol/mg protein). In the presence of isoproterenol at 3 X 10(-8) M, Bmax was increased with unaltering Kd value. Isoproterenol did not increase [3H]prostaglandin E1, [3H]prostaglandin E2 and [3H]prostaglandin F2 alpha bindings to platelets. The potential effect of isoproterenol was mimicked by forskolin, theophylline, dibutyryl cyclic AMP, prostaglandin E1 and prostaglandin I2, but it was abolished by 2', 5'-dideoxyadenosine, an inhibitor of adenylate cyclase, indicating that elevated level of cyclic AMP may be available for the induction of the increase of [3H]prostaglandin D2 binding. Prostaglandin D2-induced cyclic AMP synthesis and antiaggregation activity were also augmented in the presence of isoproterenol. These results suggest a beta 2-adrenoceptor-mediated cyclic AMP-dependent mechanism for the regulation of prostaglandin D2 receptor binding in rabbit platelets.
D000067956:Adenylyl Cyclase Inhibitors; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D000242:Cyclic AMP / Q000096:biosynthesis / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D015230:Prostaglandin D2; D011453:Prostaglandins / Q000378:metabolism; D011457:Prostaglandins D / Q000378:metabolism*; D011817:Rabbits; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000378:metabolism; D013726:Terbutaline / Q000037:antagonists & inhibitors / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D000319:Adrenergic beta-Antagonists; D011453:Prostaglandins; D011457:Prostaglandins D; D011943:Receptors, Adrenergic, beta; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D000242:Cyclic AMP; D007545:Isoproterenol; D013726:Terbutaline; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor