Functional Characterization of Human Aquaporin 9 as a Facilitative Glycerol Carrier

Autor: Hiroaki Yuasa, Kimihiko Urano, Takahiro Katano, Jun Watanabe, Megumi Ishii, Katsuhisa Inoue, Kinya Ohta, Yuriko Ohgusu
Rok vydání: 2008
Předmět:
Zdroj: Drug Metabolism and Pharmacokinetics. 23:279-284
ISSN: 1347-4367
DOI: 10.2133/dmpk.23.279
Popis: The mechanism of glycerol transport by human aquaporin 9 (hAQP9), which is a liver-specific AQP water channel and can also transport glycerol, was investigated by using the Xenopus laevis oocyte expression system. It was found that specific glycerol uptake by hAQP9 was concentration-dependent (saturable) at 25 degrees C, conforming to the Michaelis-Menten kinetics with the maximum transport rate (J(max)) of 0.84 pmol/min/oocyte and the Michaelis constant (K(m)) of 9.2 microM, and temperature-dependent, being reduced by about 70% when temperature was lowered from 25 degrees C to 4 degrees C. Such dependences on concentration and temperature are characteristic of a carrier-mediated type of mechanism rather than a channel type, which is expected not to depend on them. Furthermore, several glycerol-related compounds, such as monoacetin, were found to specifically inhibit hAQP9-mediated glycerol uptake, indicating a possibility of competition with glycerol. hAQP9-mediated glycerol uptake was, however, found not to require Na+. All these results suggest that hAQP9 functions as a facilitative carrier for glycerol, although it had been believed to function as a channel. Findings in the present study provide novel insight into its glycerol-transporting mechanism and would help exploring a possibility that hAQP9 inhibitors might help lower blood glucose level by reducing gluconeogenesis by limiting hepatic glycerol uptake.
Databáze: OpenAIRE
Externí odkaz: