Obestatin inhibits vasopressin secretion: evidence for a physiological action in the control of fluid homeostasis

Obestatin, a product of post-translational processing of the ghrelin prohormone, has been reported to act in the brain to inhibit thirst. We extended our initial studies on water drinking by examining the effects of obestatin on hypovolemia-induced water and saline drinking and vasopressin release in male rats. Intracerebroventricular administration of obestatin significantly inhibited water, but not saline (0.3 M NaCl) drinking in response to a hypovolemic challenge. Obestatin also inhibited, in a dose-related fashion, dehydration-induced vasopressin secretion without affecting plasma oxytocin levels. Vasopressin release induced by central angiotensin II administration was attenuated significantly by prior administration of obestatin. Finally, central administration of an antiserum specific to obestatin resulted in an exaggerated basal vasopressin release and an increased vasopressin response to overnight water deprivation. Antiserum treatment also resulted in significantly increased ad libitum water drinking and drinking in response to dehydration. We conclude that this product of post-translational processing of the ghrelin prohormone may be an important contributor to the physiologic regulation of fluid and electrolyte homeostasis.