Hormone modulation of the membrane NA⁺ pump in mammalian secretory epithelium and retina

Purpose. The activity of the membrane sodium pump is governed not only by the concentrations of Na⁺, inside the cell, but also is subject to longer-term modulation by certain hormones and intracellular messengers. This latter regulation is not related to de novo synthesis of Na,K-ATPase, but does require the action of protein kinases and protein phosphatases. Phosphorylation may occur on trie pump, itself, and/or on other proteins regulating pump activity or phosphorylation state. Most previous work in this area has focused on the roles of hormones acting through either protein kinase A and cAMP, or through protein kinase C. In these experiments, we describe the modulation of Na,K-ATPase by cGMP-stimulating natriuretic peptides (NP's), hormones whose receptors are found both in the anterior segment and retina. Methods. Slice preparations from bovine choroid plexus, ciliary process and retina were exposed to either ANP, BNP or CNP for 15′, and then washed to remove the hormone. Following permeabilization of slices, Na,K-ATPase V_max activity was measured under optimized conditions. Results. The natriuretic peptides had a profound and long-lasting inhibitory effect on sodium pump activity and, by using quantitative dose-response curves, it was possible to characterize the nature of the natriuretic receptor(s) present. Histochemical and biochemical studies localized enzymes associated with this path and determined that these peptides alter Na,K-ATPase through stimulation of guanylyl cyclase and a cGMP-modulation of protein phosphorylation state. Conclusion. These results provide a mechanism of action for decreases in CSF and aqueous humor production seen with NP's in secretory epithelium and also suggest a potential physiological role for NP's in the retina.