Intrarenal dopamine: a key signal in the interactive regulation of sodium metabolism.
The kidney regulates sodium metabolism with extraordinary precision and sensitivity. This is accomplished by an intricate interaction between signals from extrarenal and intrarenal sources and between anti-natriuretic and natriuretic factors. Dopamine, produced in renal proximal tubule cells, plays a central role in this interactive network. Natriuretic hormones that are released from extrarenal sources, such as atrial natriuretic peptide, mediate some of their effects via renal dopamine receptors. On the level of the tubules, dopamine acts by opposing the effects of anti-natriuretic factors, such as angiotensin II and alpha-adrenergic receptors. Sodium retention leads to an increase in renal dopamine tonus, and the natriuretic effects of dopamine are more prominent under this condition. Inhibition or down-regulation of dopamine receptors significantly attenuates the natriuretic response to salt loading. Renal dopamine is modulated by the supply of filtered L-DOPA and the metabolism of dopamine via catechol-O-methyldopamine. The importance of dopamine as a natriuretic hormone is reflected by its capacity to inhibit the majority of renal tubule sodium transporters. Notably, the activity of Na+, K+ ATPase is inhibited in most tubule segments by dopamine. Recent studies have elucidated many of the signaling pathways for renal dopamine receptors. Novel principles for homologous and heterologous sensitization of dopamine receptors have been detected that may explain some of the interaction between dopamine and other first messengers that modulate renal tubule sodium transport. A broad understanding of the renal dopamine system has become increasingly important, since there is now strong evidence from both clinical and experimental studies that dysregulation of the renal dopamine system plays a role in many forms of multigenetic hypertension.
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Karolinska Institutet, Department of Woman and Child Health, Stockholm, Sweden.
D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D006977:Hypertension, Renal / Q000503:physiopathology; D007668:Kidney / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D012079:Renal Circulation / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D012964:Sodium / Q000378:metabolism*
D012964:Sodium; D004298:Dopamine