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- Title
Cellular mechanisms for bi-directional regulation of tubular sodium reabsorption.
- Authors
Aperia, Anita; Fryckstedt, Jessica; Holtbäck, Ulla; Belusa, Roger; Xian-Jun Cheng; Eklöf, Ann-Christine; Li, Dailin; Zhang-Ming Wang; Ohtomo, Yoshiyuki; Aperia, A; Fryckstedt, J; Holtbäck, U; Belusa, R; Cheng, X J; Eklöf, A C; Li, D; Wang, Z M; Ohtomo, Y
- Abstract
The molecular mechanisms underlying the regulation of sodium excretion are incompletely known. Here we propose a general model for a bi-directional control of tubular sodium transporters by natriuretic and antinatriuretic factors. The model is based on experimental data from studies on the regulation of the activity of Na+,K+-ATPase, the enzyme that provides the electrochemical gradient necessary for tubular reabsorption of electrolytes and solutes in all tubular segments. Regulation is carried out to a large extent by autocrine and paracrine factors. Of particular interest are the two catecholamines, dopamine and norepinephrine. Dopamine is produced in proximal tubular cells and inhibits Na+,K+-ATPase activity in several tubule segments. Renal dopamine availability is regulated by the degrading enzyme, catechol-O-methyl transferase. Renal sympathetic nerve endings contain norepinephrine and neuropeptide Y (NPY). Activation of alpha-adrenergic receptors increase and activation of beta-adrenergic receptors decrease Na+,K+-ATPase activity. alpha-Adrenergic stimulation increases the Na+ affinity of the enzyme and thereby the driving force for transcellular Na+ transport. NPY acts as a master hormone by synergizing the alpha- and antagonizing the beta-adrenergic effects. Dopamine and norepinephrine control Na+,K+-ATPase activity by exerting opposing forces on a common intracellular signaling system of second messengers, protein kinases and protein phosphatases, ultimately determining the phosphorylation state of Na+,K+-ATPase and thereby its activity. Important crossroads in this network are localized and functionally defined. Phosphorylation sites for protein kinase A and C have been identified and their functional significance has been verified.
- Subjects
SODIUM in the body; EXCRETION; ADENOSINE triphosphatase; KIDNEY tubules; AUTOCRINE mechanisms; DOPAMINE
- Publication
Kidney International, 1996, Vol 49, Issue 6, p1743
- ISSN
0085-2538
- Publication type
journal article
- DOI
10.1038/ki.1996.259