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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 et al. (1994) studied this question.