Analogues of arginine vasopressin modified at position 2 with proline derivatives: selective antagonists of oxytocin in vitro

摘要

In mammals, arginine vasopressin (AVP) is mainly synthesized and released into the circulation by the magnocellular neurons of the supraoptic and paraventricular hypothalamic nuclei, with axons projecting to the pituitary [1]. Physiological effects of AVP are mediated by at least three distinct vasopressin receptor subtypes: V_(1a), known to mediate the contractile action of AVP on vascular smooth muscles and stimulate glycogenolysis in the liver; V_(1b) (V3), involved in the release of ACTH from pituitary; and V2, receptors mediating antidiuretic action in the kidney [2]. AVP also interacts with oxytocin (OT) receptors which are responsible for the galactobolic and uterotonic effects [3].