Ghrelin suppresses water intake with a different physiological significance from atrial natriuretic peptide in conscious seawater-acclimated eels

In general, ghrelin is known as one of the orexigenic (increasing appetite or food intake) hormones in mammals. However, it has also been shown that ghrelin inhibits water intake, which appears to be inconsistent with its role in the feeding response. In this study, the effect of ghrelin on water intake was comprehensively addressed using conscious seawater-acclimated eels as an experimental model for water drinking behaviour. When injected intra-arterially, ghrelin inhibited copious drinking in a dose-dependent manner without affecting arterial pressure. This effect contrasted with the inhibitory effect of atrial natriuretic peptide (ANP) on drinking, which is synchronized with a vasodepressor effect. Similarly, intra-cerebroventricular injection of ghrelin also decreased the drinking rate without affecting arterial pressure. Continuous infusion of ghrelin from the ventral aorta also decreased the drinking rate, concomitant with an increase in plasma ghrelin concentration. The inhibitory effects of ghrelin on drinking were as potent and efficacious as those of ANP. The inhibitory action was not blocked by pre-treatment with a ghrelin receptor antagonist ([D-Lys3] GHRP-6); consistently, the agonist form (GHRP-6) injected intra-arterially did not show any inhibitory effect of ghrelin when injected peripherally. These results demonstrate that ghrelin is a potent anti-dipsogen in eels without baroreflex and ANP secretion, and it is possible that ghrelin's effect might be mediated through another type of ghrelin receptor that [D-Lys3] GHRP-6 or GHRP-6 do not bind.