POLYOLS THAT ACCUMULATE IN RENAL TISSUE UNCOUPLE THE PLASMA-MEMBRANE CALCIUM-PUMP AND COUNTERACT THE INHIBITION BY UREA AND GUANIDINE-HYDROCHLORIDE

Sorbitol and mannitol, two stereoisomeric osmolytes, inhibit the ATP-d ependent Ca2+ transport in inside-out vesicles derived from basolatera l membranes from kidney proximal tubules. This inhibition (I-0.5 = 400 and 390 mM respectively) cannot be attributed to an increase in Ca2permeability, since the rate of EGTA-stimulated, Ca2+ efflux from prel oaded vesicles is not modified by these osmolytes. In the presence of 1 M sorbitol or mannitol, Ca2+ uptake is inhibited by 70 and 75%, resp ectively. Since the Ca2+-stimulated ATPase activity is unaffected, sor bitol and mannitol uncouple the Ca2+ transport from the ATPase activit y. The inhibition of Ca2+ transport by these osmolytes is reversible, since the inhibition disappears when the vesicles are preincubated wit h 1 M sorbitol or mannitol and then diluted 25-fold in reaction medium to measure Ca2+ accumulation. On the other hand, these osmolytes prot ect the (Ca2++Mg2+)ATPase from the inhibition of Ca2+ transport and AT Pase activity by urea and guanidinium. These data suggest that the hig h concentrations of polyols that renal cells accumulate during antidiu resis, may regulate Ca2+ transport across the plasma membrane. In addi tion, polyols may protect the (Ca2++Mg2+)ATPase from the deleterious s tructural effects of urea, a compound that also accumulates during ant idiuresis.