Renal dopamine receptors in health and hypertension.
During the past decade, it has become evident that dopamine plays an important role in the regulation of renal function and blood pressure. Dopamine exerts its actions via a class of cell-surface receptors coupled to G-proteins that belong to the rhodopsin family. Dopamine receptors have been classified into two families based on pharmacologic and molecular cloning studies. In mammals, two D1-like receptors that have been cloned, the D1 and D5 receptors (known as D1A and D1B, respectively, in rodents), are linked to stimulation of adenylyl cyclase. Three D2-like receptors that have been cloned (D2, D3, and D4) are linked to inhibition of adenylyl cyclase and Ca2+ channels and stimulation of K+ channels. All the mammalian dopamine receptors, initially cloned from the brain, have been found to be expressed outside the central nervous system, in such sites as the adrenal gland, blood vessels, carotid body, intestines, heart, parathyroid gland, and the kidney and urinary tract. Dopamine receptor subtypes are differentially expressed along the nephron, where they regulate renal hemodynamics and electrolyte and water transport, as well as renin secretion. The ability of renal proximal tubules to produce dopamine and the presence of receptors in these tubules suggest that dopamine can act in an autocrine or paracrine fashion; this action becomes most evident during extracellular fluid volume expansion. This renal autocrine/paracrine function is lost in essential hypertension and in some animal models of genetic hypertension; disruption of the D1 or D3 receptor produces hypertension in mice. In humans with essential hypertension, renal dopamine production in response to sodium loading is often impaired and may contribute to the hypertension. The molecular basis for the dopaminergic dysfunction in hypertension is not known, but may involve an abnormal post-translational modification of the dopamine receptor.
Jose
P A
PA
Department of Pediatrics, Georgetown University Medical Center, Washington, DC 20007, USA.
Eisner
G M
GM
Felder
R A
RA
D000818:Animals; D004298:Dopamine / Q000378:metabolism / Q000502:physiology; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism; D011954:Receptors, Dopamine / Q000145:classification / Q000502:physiology*; D012079:Renal Circulation / Q000502:physiology; D012964:Sodium / Q000493:pharmacokinetics
D011954:Receptors, Dopamine; D012964:Sodium; D004298:Dopamine