The vasopressin receptor antagonist dPTyr (Me) AVP does not prevent stress-induced ACTH and corticosterone release.

Abstract

Most of the experimental evidence for a role of arginine-vasopressin (AVP) in adrenocorticotropic hormone (ACTH) release comes from in vitro studies. The multimolecular nature of the hypothalamic factor responsible for corticotropin (CRF) release has long been recognized, but the importance of AVP as a cofactor is controversial. The recently characterized 41-residue peptide fulfills the criteria for a physiological role in ACTH release and it is potentiated in vitro by AVP. In vivo, AVP is able to stimulate ACTH secretion, and Brattleboro rats, deficient in AVP, show a reduced activity of the hypothalamo-hypophysial-adrenocortical system (HHCS) (see ref. 13 for references). Direct evidence for involvement of AVP in the physiological release of ACTH is, however, still lacking. The recent development of AVP receptor antagonists provides the opportunity to test this hypothesis directly. I report here that pretreatment by 1-deaminopenicillamine, 2-(O-methyl)tyrosine arginine-vasopressin (dPTyr(Me)AVP), a potent antagonist of the vasopressor, behavioural and ACTH-releasing properties of AVP, does not modify the ACTH and corticosterone secretion induced by exposure to a novel environment, but totally inhibits the increase of ACTH and corticosterone levels induced by AVP. The results do not support the hypothesis for a physiological involvement of AVP in ACTH release.