Na+/myo-inositol cotransport is regulated by tonicity in cultured rat mesangial cells

Mesangial cells are considered to be faced with osmotic stress under physiological (such as extraglomerular mesangial cells) and pathophysiological (for example, diabetes mellitus) conditions. To see if mesangial cells have an osmoregulatory mechanism, like renal medullary cells, we measured the intracellular contents of organic osmolytes in isotonic and hypertonic conditions. Cultured rat mesangial cells are well tolerant of acute increase in osmolality up to 500 mOsm/kg. The myo-inositol content increased in hypertonic cells more than six-fold the value in isotonic cells. The contents of glycerophosphorylcholine and sorbitol also increased but were less than that of myo-inositol. The Na(+)-dependent myo-inositol uptake in hypertonic cells was a 12-fold uptake in isotonic cells, reaching a maximum 24 hours after the switch to a hypertonic medium. The uptake rate increased as medium osmolality increased from 300 to 500 mOsm/kg. Raffinose is the most effective solute to increase the myo-inositol uptake. NaCl, glucose and mannitol also increased the uptake rate (NaCl > glucose > mannitol). The increased uptake by hypertonicity was the result of an increase in Vmax without change in Km and was dependent on RNA and protein synthesis. These results indicate that mesangial cells respond to extracellular hypertonicity by increasing myo-inositol transport activity and accumulating myo-inositol into the cells, suggesting that myo-inositol functions as an organic osmolyte in mesangial cells.