Obestatin Inhibits Vasopressin Release and Thirst

Abstract

We have previously reported that obestatin, a product of post-translational processing of the ghrelin prohormone, significantly inhibits thirst in a variety of animal models (AJP 292:, 2007). To further investigate potential CNS actions of obestatin on fluid and electrolyte homeostasis, we examined the effects of i.c.v. administration of the peptide on salt appetite and vasopressin (AVP) secretion. Saline drinking in response to polyethylene glycol-induced hypovolemia was not altered by obestatin in a dose that did significantly reduced water drinking in this and previously reported models. On the other hand, i.c.v. administration of obestatin in overnight water restricted rats significantly reduced AVP levels in peripheral plasma in a time and dose-dependent fashion. Our previous patch clamp recordings have shown that subfornical organ neurons respond to the direct application of obestatin, and thus the actions of the peptide may occur as a consequence of actions at circumventricular organs and not the hypothalamus. These results further our hypothesis that obestatin acts within the CNS to modulate the behavioral and endocrine mechanisms controlling fluid balance.