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Sorbitol and mannitol, two stereoisomeric osmolytes, inhibit the ATP-dependent Ca 2+  transport in inside-out vesicles derived from basolateral membranes from kidney proximal tubules. This inhibition (I 0,5  = 400 and 390 mᴍ respectively) cannot be attributed to an in­ crease in Ca 2+  permeability, since the rate of EGTA-stimulated Ca 2+  efflux from preloaded vesicles is not modified by these osmolytes. In the presence of 1 ᴍ sorbitol or mannitol, Ca 2+  uptake is inhibited by 70 and 75%, respectively. Since the Ca 2+ -stimulated ATPase activity is unaffected, sorbitol and mannitol uncouple the Ca 2+  transport from the ATPase activity. The inhibition of Ca 2+  transport by these osmolytes is reversible, since the inhibition dis­appears when the vesicles are preincubated with 1 ᴍ sorbitol or mannitol and then diluted 25-fold in reaction medium to measure Ca 2+  accumulation. On the other hand, these osmo­lytes protect the (Ca 2+  +Mg 2+ )ATPase from the inhibition of Ca 2+  transport and ATPase activity by urea and guanidinium. These data suggest that the high concentrations of polyols that renal cells accumulate during antidiuresis, may regulate Ca 2+  transport across the plasma membrane. In addition, polyols may protect the (Ca 2+  + Mg 2+ ) ATPase from the deleterious structural effects of urea, a compound that also accumulates during antidiuresis.

Polyols that Accumulate in Renal Tissue Uncouple the Plasma Membrane Calcium Pump and Counteract the Inhibition by Urea and Guanidine Hydrochloride