Renal dopamine system: Function, Metabolism and Regulation

CHOI MR; LEE BM; FERNÁNDEZ BE

Dopamine: Functions, Regulation and Health Effects

Nova Science Publishers

Lugar: New York; Año: 2012; p. 1 - 48

Diverse endocrine, autocrine and neuronal factors are involved in blood pressure regulation. Some of them can regulate renal functions like sodium metabolism through direct mechanisms that involve the control of sodium transporters or through indirect mechanisms that mediate renal dopamine (DA) handling. Sodium metabolism constitutes a key target for blood pressure regulation and the kidneys play a fundamental role in this process. In 1964 it was found that DA increases the glomerular filtration rate and sodium excretion, acting as a relevant autocrine and paracrine regulator of renal functions. Endogenously sinthesized DA by the kidneys contributes to regulate some of renal functions.  The kidney has all the enzymatic machinery to synthesize and catabolize DA. The main source of renal DA are the proximal tubular cells, which have a high concentration of the enzyme L -Dopa decarboxylase and may also uptake DA from the blood or the lumen by means of extraneuronal uptake transporters of DA, such as the organic cation transporters. Renal DA catabolism is mediated by monoamine oxidase (MAO) and catechol-o-methyl transferase (COMT). The activities of both enzymes are high in renal tissues, being COMT abundantly expressed in proximal tubular cells. However, deamination by MAO seems to be the major catabolic pathway for renal DA. DA effects on renal sodium handling are mediated through both D1-like and D2-like receptors. The activation of these receptors induces a large increase in urinary sodium excretion, which is dependent of Na+, K+-ATPase activity inhibition, as well as of diverse sodium influx pathways in proximal and distal tubular cells. Therefore, those factors that modulate intrarenal levels of DA, also affect the regulation of sodium metabolism. In addition, renal DA interacts together with other natriuretic hormones and/or antagonizes the effects of antinatriuretic agents. All these effects takes place at different renal levels, and include different mechanisms such as recruitment/internalization or sensibilization/desensibilization of receptors, activation/deactivation of enzymes, signaling trafficking and regulation of sodium transporter activities, like Na+/H+ antiporter, Na+/HCO3- co-transporter, Na+-ATPase and Na+, K+-ATPase enzyme. Antinatriuretic factors like angiotensin II or norepinephrine, and natriuretic factors like atrial natriuretic peptide, urodilatin, prolactin and prostaglandins may modulate renal DA metabolism, contributing to a fine equilibrium of sodium reabsorption and excretion, allowing the maintenance of adequate urinary fluid and equilibrated electrolyte balance to reach normal blood pressure levels.