Dual effect of cyclic GMP on renal brush border Na-H antiporter.
The Na-H antiporter of renal-brush border membranes is inhibited by cyclic AMP and stimulated by protein kinase C. The proximal tubule contains guanylate cyclase and is capable of cyclic GMP production. The effect of cGMP on renal Na-H antiporter activity was analyzed in phosphorylated brush border membranes by 22Na uptake in the presence or absence of 1 mM amiloride. 8-Bromo cyclic GMP (1 microM) increased the amiloride-sensitive 22Na uptake in control from 1.26 +/- 0.13 to 1.54 +/- 0.12 nmol/mg/protein/10 sec, P less than 0.01, without altering the amiloride-insensitive component. In the absence of exogenous ATP, cGMP also stimulated the amiloride-sensitive 22Na uptake, which can be explained by the presence of endogenous ATP in concentrations of up to 50 microM in the membranes. In ATP-depleted membrane vesicles, however, cGMP inhibited the amiloride-sensitive 22Na uptake. These data indicate that cGMP acts on the Na-H antiporter by at least two different mechanisms, one of which is ATP dependent. It is likely that cGMP-dependent protein kinase mediates the stimulatory effects seen in the presence of ATP, and the inhibition seen in ATP-depleted membranes results from cGMP direct action on the Na-H antiporter.
Green
M
M
Section of Nephrology, University of Illinois, Chicago 60612.
Ruiz
O S
OS
Kear
F
F
Arruda
J A
JA
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002352:Carrier Proteins / Q000032:analysis*; D006152:Cyclic GMP / Q000494:pharmacology*; D066298:In Vitro Techniques; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008871:Microvilli / Q000378:metabolism; D010766:Phosphorylation; D011817:Rabbits; D012964:Sodium / Q000378:metabolism; D017923:Sodium-Hydrogen Exchangers
D001639:Bicarbonates; D002352:Carrier Proteins; D008565:Membrane Proteins; D017923:Sodium-Hydrogen Exchangers; D000255:Adenosine Triphosphate; D012964:Sodium; D006152:Cyclic GMP