Tsushima Hiromi, Mori Mayumi
Department of Cellular and Molecular Pharmacology, Nagoya City University, Japan.
Am J Physiol Regul Integr Comp Physiol. 2006 Jun;290(6):R1736-41. doi: 10.1152/ajpregu.00043.2005. Epub 2006 Jan 26.
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.
瞬时受体电位香草酸亚型4（TRPV4）是瞬时受体电位（TRP）超家族中非选择性阳离子通道的成员之一。最近，有人提出TRPV4可能是一种渗透压感受器，因为它存在于推测有渗透压感受器分布的室周器官中，并且在体外实验中对渗透压敏感。此外，TRPV4基因敲除小鼠具有异常的渗透压敏感性。在本研究中，研究了TRPV4激动剂4α-佛波醇12,13-十二烷酸酯（4α-PDD）对野生型动物体内饮水行为的影响，以探讨TRPV4作为渗透压感受器的作用。脑室内注射4α-PDD在正常条件下的白天和黑夜、禁食后以及注射血管紧张素II后均抑制水摄入。然而，该药物对高渗溶液注射后或禁水后导致血浆渗透压显著升高时的饮水增加没有影响。与注射溶剂的组相比，注射4α-PDD组的运动活性略有下降；然而，两组之间的甜味觉、食物摄入量和体温没有差异。TRPV4拮抗剂如钌红或钆预先注射到脑室可阻断4α-PDD的抗饮水作用。这些发现表明，TRPV4在某些条件下调节饮水行为，并且这种调节与血管紧张素II途径相互作用。
