Effects of inhibition of myo-inositol transport on mdck cells under hypertonic environment. Kitamura, Hiroshi, Atsushi Yamauchi, Takeshi Nakanishi, Yoshihiro Takamitsu, Toshihiro Sugiura, Akiko Akagi, Toshiki Moriyama, Masaru Horio, Enyu Imai. First Department of Medicine, and Department of Clinical Laboratory Science, Osaka University School of Medicine, Suita, 565, Japan; and Faculty of Health and Sport Sciences, Osaka University, Suita, 565, Japan; and Department of Kidney and Dialysis, Hyogo College of Medicine, Nishinomiya, 663, Japan
APStracts 3:0201F, 1996.
In order to investigate the role of myo-inositol under hypertonic conditions, we examined the effects of inhibition of myo-inositol transport in Madin-Darby canine kidney (MDCK) cells using an analogue of myo-inositol, 2-O,C-methylene-myo-inositol (MMI). We first characterized the inhibitory effects of MMI on myo-inositol transport in MDCK cells. The Na+-dependent component of [3H] myo-inositol uptake was inhibited by MMI in a concentration-dependent manner, although MMI did not inhibit the activities of the betaine transporter and system A neutral amino acid transporter. We found decreased affinity for myo-inositol in the presence of MMI whereas the Vmax of the transporter did not change. Thus, MMI behaves as a competitive inhibitor of myo-inositol transport with a relatively high Ki value (1.6 mM). Myo-inositol content in hypertonic MDCK cells was markedly reduced in the presence of 5 mM MMI, but MMI itself did not accumulate in these cells. The hypertonic cells began to detach in the presence of MMI 3 days after increasing medium osmolality, whereas MMI did not affect the cells in isotonic medium. We also examined the effects of MMI on colony-forming efficiency of MDCK cells. MMI decreased colony-forming efficiency in a concentration -dependent manner and addition of myo-inositol returned the efficiency to the value without MMI. Addition of betaine also increased colony -forming efficiency in the presence of MMI. These results indicate that myo-inositol plays an important role in survival and growth under hypertonic environment. 

Received 17 July 1996; accepted in final form 24 October 1996.
APS Manuscript Number F203-6.
Article publication pending Am. J. Physiol. (Renal Fluid Electrolyte
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996