Analysis of the dual mechanism of ACTH release by arginine vasopressin and its analogs in conscious rats.
Plasma ACTH and/or corticosterone levels were measured in conscious rats 30 min after subcutaneous administration of arginine vasopressin (AVP), oxytocin (OT) and various analogs with a large range of activity on the vasopressor (V1), antidiuretic (V2) or oxytocic receptors. The comparison of their dose-response curves indicated that two different mechanisms are involved in the release of ACTH by neurohypophysial peptides and their analogs. AVP itself and a specific vasopressor agonist (Phe2, Orn8, OT) displayed a similar, high slope dose-response curve. Non-vasopressor analogs, such as dDAVP were characterized by a low slope dose-response curve. Furthermore, dDAVP potentiated CRF and neither its own ACTH-releasing action nor its potentiation of CRF were sensitive to previous VI- or V2-receptor blockade. These results, together with other available data, are interpreted as indicative of the existence of two mechanisms of action for ACTH release by AVP and its analogs in vivo: an indirect action via endogenous CRF release, mediated by a VI receptor mechanism, and a direct action on the pituitary, shared by dDAVP and other non-vasopressor analogs, with receptor characteristics different to both the V1 and the V2 classical types.
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D001127:Arginine Vasopressin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology; D004231:Diuresis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects*; D011956:Receptors, Cell Surface / Q000187:drug effects*; D017483:Receptors, Vasopressin; D013329:Structure-Activity Relationship
D011945:Receptors, Angiotensin; D011956:Receptors, Cell Surface; D017483:Receptors, Vasopressin; D001127:Arginine Vasopressin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone