Some characteristics of GnRH receptors in rat-pituitary membranes: differences between an agonist and and antagonist.
The interaction of gonadotropin-releasing hormone (GnRH) agonists and antagonists with pituitary membranes was studied by using 125I-labeled agonist, [D-Ser(t-Bu)6, des-Gly10-ethylamide]-GnRH, and antagonist [D-pGlu1, D-Phe2, Trp3,6]-GnRH. Their binding was affected differently by cations, and by pretreatment of membranes with proteolytic enzymes and sulfhydryl-blocking reagents. Monovalent cations at millimolar concentrations (10-100 mM) and divalent cations at lower concentrations (0.5-5 mM) reduced more significantly the binding of the agonist than that of the antagonist. Pretreatment of the membranes with trypsin and chymotrypsin abolished the specific binding of both agonist and antagonist, in a dose-response manner, with the former being less affected. Pretreatment of the membranes with sulfhydryl-blocking reagents did not alter the binding of the antagonist but enhanced the binding of the agonist. This enhancement in the specific binding was found to be due to an increase in the apparent affinity of the agonist. These results may suggest that GnRH agonists and antagonists bind differently to the same receptor.
D000818:Animals; D002064:Buserelin; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000378:metabolism; D002918:Chymotrypsin / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006728:Hormones / Q000378:metabolism*; D007461:Iodoacetates / Q000494:pharmacology; D019807:Iodoacetic Acid; D008274:Magnesium / Q000494:pharmacology; D010902:Pituitary Gland / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011966:Receptors, LHRH; D012964:Sodium / Q000494:pharmacology; D014357:Trypsin / Q000378:metabolism
D006728:Hormones; D007461:Iodoacetates; D011956:Receptors, Cell Surface; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D012964:Sodium; D002918:Chymotrypsin; D014357:Trypsin; D008274:Magnesium; D002064:Buserelin; D011188:Potassium; D002118:Calcium; D019807:Iodoacetic Acid