OXYTOCIN-STIMULATED RELEASE OF ADRENOCORTICOTROPIN FROM THE RAT PITUITARY IS MEDIATED BY ARGININE-VASOPRESSIN RECEPTORS OF THE V-1B TYPE

Previous work showed the existence of receptors for arginine vasopress in (AVP) in the anterior pituitary; these receptors were classified as belonging to a distinct AVP receptor subtype, referred to as AVP-V-1b receptors, and are thought to mediate the well documented ACTH-releas ing activity of AVP. In the present work, high affinity receptors for another neurohypophyseal hormone, oxytocin (OT), were also shown to be present within the rat anterior pituitary; to this end, [I-125]d(CH2) (5)[Tyr(Me)(2)Thr(4)Tyr-NH29]OVT was used as a ligand in receptor bind ing studies. Experiments on dispersed rat anterior pituitary cells in a superfusion system confirmed earlier reports that OT acts as an addi tional secretagogue of ACTH, with significant effects first seen at co ncentrations as low as 1 nM. Further studies addressed the question of whether stimulation of ACTH release is mediated by OT receptors or wh ether receptors for AVP (V-1b receptors) might serve this role. For th is, highly selective agonist and antagonist ligands of the OT receptor and nonselective agonist and antagonist ligands of the V-1b receptor were employed. Neither the OT receptor agonist Thr(4)Gly(7)OT nor the OT receptor antagonist des-Gly(NH2)(9)d(CH2)(5)-[Tyr(Me)(2)Thr(4)]OVT displayed any influence on basal ACTH release, and des-Gly(NH2)(9)d(CH 2)(5)-[Tyr(Me)(2)Thr(4)] OVT did not interfere with OT-induced ACTH re lease; these results indicated that OT promotes ACTH release through a receptor(s) other than the OT receptor itself Evidence for the involv ement of AVP V-1b receptors was provided by the observation that the A VP receptor antagonist dP[Tyr(Me(2))]AVP completely abolished OT-elici ted increases in ACTH release. Thus, AVP V-1b receptors mediate the ac tions of two structurally related peptides on ACTH secretion; the role of OT receptors in adenohypophyseal function remains to be determined .