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-dependent Ca2+ transport in inside-out vesicles derived from basolateral membranes from kidney proximal tubules. This inhibition (I0.5 = 400 and 390 mM respectively) cannot be attributed to an increase in Ca2+ permeability, since the rate of EGTA-stimulated Ca2+ efflux from preloaded vesicles is not modified by these osmolytes. In the presence of 1 M sorbitol or mannitol, Ca2+ uptake is inhibited by 70 and 75%, respectively. Since the Ca(2+)-stimulated ATPase activity is unaffected, sorbitol and mannitol uncouple the Ca2+ transport from the ATPase activity. The inhibition of Ca2+ transport by these osmolytes is reversible, since the inhibition disappears when the vesicles are preincubated with 1 M sorbitol or mannitol and then diluted 25-fold in reaction medium to measure Ca2+ accumulation. On the other hand, these osmolytes protect the (Ca2+ + Mg2+) ATPase from the inhibition of Ca2+ 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 Ca2+ transport across the plasma membrane. In addition, polyols may protect the (Ca2+ + Mg2+) ATPase from the deleterious structural effects of urea, a compound that also accumulates during antidiuresis.
Sola-Penna
M
M
Departamento de Bioquímica Médica, Universidade Federal do Rio de Janeiro, Brasil.
Lemos
A dos P
Ados P
Fávero-Retto
M P
MP
Meyer-Fernandes
J R
JR
Vieyra
A
A
D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004533:Egtazic Acid / Q000494:pharmacology; D019791:Guanidine; D006146:Guanidines / Q000494:pharmacology*; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D007700:Kinetics; D008353:Mannitol / Q000378:metabolism / Q000494:pharmacology*; D012756:Sheep; D013012:Sorbitol / Q000378:metabolism / Q000494:pharmacology*; D014508:Urea / Q000494:pharmacology*
D006146:Guanidines; D008353:Mannitol; D013012:Sorbitol; D004533:Egtazic Acid; D014508:Urea; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases; D019791:Guanidine; D002118:Calcium