Effects of inhibition of myo-inositol transport on MDCK cells under hypertonic environment

Am J Physiol. 1997 Feb;272(2 Pt 2):F267-72. doi: 10.1152/ajprenal.1997.272.2.F267.


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 analog 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 maximal velocity (Vmax) of the transporter did not change. Thus MMI behaves as a competitive inhibitor of myo-inositol transport with a relatively high inhibition constant (K(i)) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Transport / drug effects
  • Cell Division / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Dogs
  • Hypertonic Solutions / pharmacology*
  • Inositol / analogs & derivatives
  • Inositol / antagonists & inhibitors
  • Inositol / metabolism*
  • Inositol / pharmacology
  • Kidney / cytology
  • Kidney / drug effects
  • Kidney / metabolism*


  • Hypertonic Solutions
  • Inositol