Antidipsogenic effects of a TRPV4 agonist, 4alpha-phorbol 12,13-didecanoate, injected into the cerebroventricle

Transient receptor potential vanilloid 4 (TRPV4) is one member of the TRP superfamily of nonselective cation channels. Recently, the possibility has been raised that TRPV4 is an osmoreceptor, because it is found in the circumventricular organs where osmoreceptors are supposed to be distributed and because it is sensitive to osmotic pressure in in vitro experiments. In addition, TRPV4 knockout mice have abnormal osmosensitivity. In this study, effects of 4alpha-phorbol 12,13-didecanoate (4alpha-PDD), a TRPV4 agonist, on drinking behavior were examined to investigate roles for TRPV4 as an osmoreceptor in vivo in wild-type animals. Intracerebroventricular injections of 4alpha-PDD inhibited water intake under normal conditions in both light and dark periods of the day, after food deprivation, and after administration of angiotensin II. However, this drug did not influence increased water intake after administration of a hypertonic solution or after water deprivation that significantly increased plasma osmolality. Locomotor activity of the 4alpha-PDD-injected group decreased slightly compared with that of the vehicle-injected group; however, sweet taste, food intake, and body temperature were not different between the two groups. The antidipsogenic effects of 4alpha-PDD were blocked by preinjection into the ventricle of TRPV4 antagonists such as ruthenium red or gadolinium. These findings suggest that TRPV4 regulates drinking behavior under certain conditions, and the regulation interacts with the angiotensin II pathway.