| Co-Investigator(Kenkyū-buntansha) |
EGUCHI Takafumi The University of Tokushima, Sch. of Dentistry, Research Associate, 歯学部, 助手 (90263847)
MARCHLIK Wojciech The University of Tokushima, Sch. of Dentistry, Research Associate, 歯学部, 助手 (00335803)
ISHIDA Hajime The University of Tokushima, Sch. of Dentistry, Professor, 歯学部, 助教授 (70028364)
IMAI Yasuo The University of Tokushima, Sch. of Dentistry, Research Associate, 歯学部, 助手 (30271068)
SKOWRONSKI Mariusz The University of Tokushima, Sch. of Dentistry, Research Associate, 歯学部, 助手 (00294702)
|
|---|
| Research Abstract |
The stimulatory effect of acetylcholine, but not that of epinephrine, on the abundance of aquaporin-5 in the apical plasma membrane (APM) of parotid acinar cells was markedly reduced in tissue from senescent rats relative to that in tissue from young adult animals. In this study, we looked for the drug which persistent increase in the amount AQP5 in the APM of-parotid glands of senescent rats.
cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinuclidine induced a marked increase of AQP5 in the APM of parotid tissues in a dose-dependent manner with an EC_<50> value of 14.2 ± 2.3 nM. cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinuclidine- and pilocarpine-induced increase in the amount of AQP5 in the APM was maximal at 10 and 3 min, respectively, and persisted for longer than 30 min. This increase was inhibited by pF-HHSiD, U73122, dantrolene or TMB-8, but not by GF 109203X. In the presence of extracellular CaCl_2, cis-2-methylspiro- (1,3- oxathiolane-5,3')-quinuclidine induced marked and persistent oscillations in [ Ca^<2+> ]i in isolated acinar cells. These results suggest that cis-2-methylspiro-(1,3- oxathiolane-5,3')-quinuclidine acts at M_3 receptors to induce a persistent increase in the amount of AQP5 in APM of parotid acini, and that this effect is mediated by the release of Ca^<2+> from intracellular stores through both inositol 1,4,5-trisphosphate and ryanodine receptors.
The cis-2-methylspiro-(1,3-oxathiolane-5,3')-quinuclidine induced a persistent increase in the amount of aquaporin-5 in the apical plasma membrane that was similar for parotid tissue from young adult and senescent rats, suggesting that this drug prove effective for treatment of age-related xerostomia.
|
