VASOPRESSIN-BINDING SITES IN THE PIG PITUITARY-GLAND - COMPETITION BYNOVEL VASOPRESSIN ANTAGONISTS SUGGESTS THE EXISTENCE OF AN UNUSUAL RECEPTOR SUBTYPE IN THE ANTERIOR LOBE

Arginine vasopressin (AVP) acts in the pituitary gland, in synergy wit h corticotrophin-releasing factor, to induce ACTH release in response to stressful stimuli. Pituitary AVP receptors in the rat are coupled t o phospholipase C, as are the so-called V-1-type AVP receptors. The pr esent study examined [H-3]AVP binding in membranes prepared from the a nterior lobe of the pituitary gland of the pig. [H-3]AVP, alone or in competition with analogues, bound to sites in the pig anterior lobe wh ich are pharmacologically similar to those described previously by oth ers in the rat pituitary gland. For comparison, the same competition s tudies were performed on membrane preparations from the rat liver whic h contain the classic V-1-type AVP receptor. Pituitary and liver AVP-b inding sites were dissimilar; both cyclic and linear V-1 antagonists h ad, in general, a much lower affinity for pituitary AVP-binding sites than for those in the liver. Thus, Phaa-D-Tyr(Et)-Phe-GLn-Asn-Lys-Pro- Arg-NH2, (Phaa = phenylacetyl) has a 2500-fold greater affinity for th e latter (negative logarithm of inhibition constant (pK(i))= 9.64) tha n for the former (pK(i) = 6.22). One linear antagonist, Pa-D-Tyr-Phe-V al-Asn-Arg-Pro-Arg-Arg-NH2, (Pa = propionyl) had about equal affinitie s for Liver and pituitary membranes (pK(i) = 6.39 and 6.53 respectivel y). Another compound, Phaa-D-Tyr-Phe-Val-Asn-Arg-Pro-Arg-Arg-NH2 had t he highest affinity found to date for binding to AVP sites in the pitu itary (pK(i) = 7.43). These findings suggest some ideas for the design of more potent and/or selective AVP analogues acting in the pituitary gland.