NA+ MYO-INOSITOL COTRANSPORT IS REGULATED BY TONICITY IN CULTURED RATMESANGIAL CELLS/

Mesangial cells are considered to be faced with osmotic stress under p hysiological (such as extraglomerular mesangial cells) and pathophysio logical (for example, diabetes mellitus) conditions. To see if mesangi al cells have an osmoregulatory mechanism, like renal medullary cells, we measured the intracellular contents of organic osmolytes in isoton ic and hypertonic conditions. Cultured rat mesangial cells are well to lerant of acute increase in osmolality up to 500 mOsm/kg. The myo-inos itol content increased in hypertonic cells more than six-fold the valu e in isotonic cells. The contents of glycerophosphorylcholine and sorb itol also increased but were less than that of myo-inositol. The Na+-d ependent myo-inositol uptake in hypertonic cells was a 12-fold uptake in isotonic cells, reaching a maximum 24 hours after the switch to a h ypertonic medium. The uptake rate increased as medium osmolality incre ased from 300 to 500 mOsm/kg. Raffinose is the most effective solute t o increase the myo-inositol uptake. NaCl, glucose and mannitol also in creased the uptake rate (Nacl > glucose > mannitol). The increased upt ake by hypertonicity was the result of an increase in V-max without ch ange in Km and was dependent on RNA and protein synthesis. These resul ts indicate that mesangial cells respond to extracellular hypertonicit y by increasing myo-inositol transport activity and accumulating myo-i nositol into the cells, suggesting that myo-inositol functions as an o rganic osmolyte in mesangial cells.