NITRIC-OXIDE, CGMP, AND HORMONE REGULATION OF ACTIVE SODIUM-TRANSPORT

The inter- and intracellular regulator nitric oxide (NO) has been sugg ested to play a role in the modulation of cellular excitability, but t he mechanism(s) by which this occurs remain unclear. Using the kidney as a model system, we report here evidence that NO, produced in respon se 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, invol ves cGMP and cGMP-dependent protein kinase. Na,K-ATPase can also be re gulated by alterations of cGMP initiated through NO-independent factor s, such as atriopeptin, and in nonrenal tissues, such as cerebellum. R egulation of the membrane sodium pump by NO and cGMP, therefore, repre sents a mechanism for hormonal modulation of ion gradients, not only i n kidney but also in other organs, including brain, where NO and cGMP play a prominent role in cellular function.