抄録
TRPV4 is first reported to be a "hypoosmolality-sensing" cation channel. On the following studies with knockout mice (Trpv4-/-), we have reported that response of vasopressin to hypertonicity was exaggerated but another group has reported that it was abolished in Trpv4-/-. Although controversial in response, both reports suggest that TRPV4 can be responsible to hypertonic stimuli. To elucidate "hyperosmolality-sensing" in TRPV4, we designed to re-examine the response in vivo and investigate whether TRPV4 was sensitive to hyperosmolality in cultured neuronal cells. Trpv4-/- and Trpv4+/+ mice were subjected to dehydration from 24 to 96 hrs. Then serum osmolality and water intake were measured. There was not remarkable difference in serum osmolality at any period of dehydration but a significant decrease in serum osmolality of Trpv4-/- at 72 hrs dehydration. Water-crave behavior and amount of water intakes after the dehydrations were not changed. Thus TRPV4 channel may respond to hyperosmolality. Neuronal cell lines with and without TRPV4 were established from a cell line. Hyperosmoliality (500 mOsm) induced robust Ca influx in TRPV4 (+) cells by the method of fluorescence quenching, while not in TRPV4 (-) cells. The influx was partially blocked with genistine, a blocker of tyrosine kinase, and blunted with pBPB, a blocker of PLA2. Therefore, TRPV4 is hyperosmolality-sensng channel through several biochemical cascades. [J Physiol Sci. 2006;56 Suppl:S90]
