Is the renal (Na + K)-ATPase modulated by intracellular messengers?
The basic cellular mechanisms involved in the regulation of (Na + K)-ATPase are discussed. Various ligands seem to be responsible for the short-term modulation of this enzyme activity (intracellular messengers). Cytosolic Ca2+ has a key role in mediating changes induced by hormones or receptor agonist; but, in turn, intracellular Ca(2+)-dependent proteins like calmodulin, calnaktin or others, are also needed for these changes. Phosphorylation of effector proteins, following the activation of PKC, PKA or CaM-kinase II, may result in changes of (Na + K)-ATPase activity either by a direct effect on the catalytic subunit or by modulating the Na(+)-H+ exchanger thereby resulting in an effect on intracellular sodium, whose concentration is known to be rate-limiting for the enzyme activity. Despite the ubiquity of (Na + K)-ATPase in various organs and tissues, its response to modulators partly depends on the heterogeneity of the alpha-subunit that give rise to the existence of different isoforms. The relative abundance of alpha 1, alpha 2, alpha 3 or other isoforms is tissue-specific and represents another way of regulation among different cell types. While these cellular mechanisms occur in various cell types the kidney shows an opposite response respect to other tissues such as liver or brain. The functional relevance of the mechanisms of acute adaptation of (Na + K)-ATPase, discussed in this review, is becoming increasingly recognized for the renal enzyme, what may contribute to stimulate new approaches to the study of the short-term regulation of the pump activity in molecular terms.
Rodrigo
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R
Departamento de Medicina Experimental, Facultad de Medicina, Universidad de Chile, Santiago.
Novoa
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E
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D004298:Dopamine / Q000494:pharmacology; D004789:Enzyme Activation; D006801:Humans; D007668:Kidney / Q000201:enzymology*; D009318:Natriuresis / Q000187:drug effects; D011458:Prostaglandins E / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D011458:Prostaglandins E; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium; D004298:Dopamine