Nitric oxide, cGMP, and hormone regulation of active sodium transport.
The inter- and intracellular regulator nitric oxide (NO) has been suggested to play a role in the modulation of cellular excitability, but the mechanism(s) by which this occurs remain unclear. Using the kidney as a model system, we report here evidence that NO, produced in response to various hormones and cytokines, can effect long-term alterations in the activity of the membrane sodium pump. This regulation of Na, K-ATPase, which occurs in a system of NO-containing renal tubules, involves cGMP and cGMP-dependent protein kinase. Na, K-ATPase can also be regulated by alterations of cGMP initiated through NO-independent factors, such as atriopeptin, and in nonrenal tissues, such as cerebellum. Regulation of the membrane sodium pump by NO and cGMP, therefore, represents a mechanism for hormonal modulation of ion gradients, not only in kidney but also in other organs, including brain, where NO and cGMP play a prominent role in cellular function.
McKee
M
M
Department of Neurology, Harvard Medical School, Charlestown, MA.
Scavone
C
C
Nathanson
J A
JA
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D000818:Animals; D001693:Biological Transport, Active; D002460:Cell Line; D002531:Cerebellum / Q000201:enzymology; D006152:Cyclic GMP / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D007672:Kidney Cortex / Q000378:metabolism; D007679:Kidney Medulla / Q000201:enzymology; D007684:Kidney Tubules / Q000201:enzymology; D007700:Kinetics; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013552:Swine
D007527:Isoenzymes; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase; D000254:Sodium-Potassium-Exchanging ATPase; D006152:Cyclic GMP