Dopamine receptors and hypertension.
Dopamine plays an important role in regulating renal function and blood pressure. Dopamine synthesis and dopamine receptor subtypes have been shown in the kidney. Dopamine acts via cell surface receptors coupled to G proteins; the receptors are classified via pharmacologic and molecular cloning studies into two families, D1-like and D2-like. Two D1-like receptors cloned in mammals, the D1 and D5 receptors (D1A and D1B in rodents), are linked to adenylyl cyclase stimulation. Three D2-like receptors (D2, D3, and D4) have been cloned and are linked mainly to adenylyl cyclase inhibition. Activation of D1-like receptors on the proximal tubules inhibits tubular sodium reabsorption by inhibiting Na/H-exchanger and Na/K-adenosine triphosphatase activity. Reports exist of defective renal dopamine production and/or dopamine receptor function in human primary hypertension and in genetic models of animal hypertension. In humans with essential hypertension, renal dopamine production in response to sodium loading is often impaired and may contribute to hypertension. A primary defect in D1-like receptors and an altered signaling system in proximal tubules may reduce dopamine-mediated effects on renal sodium excretion. The molecular basis for dopamine receptor dysfunction in hypertension is being investigated, and may involve an abnormal posttranslational modification of the dopamine receptor.
Banday
Anees Ahmad
AA
Heart and Kidney Institute, College of Pharmacy, University of Houston, 4800 Calhoun Road, Houston, TX 77204, USA. abanay@uh.edu
Lokhandwala
Mustafa F
MF
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology / Q000652:urine; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D009318:Natriuresis / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D011954:Receptors, Dopamine / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D002316:Cardiotonic Agents; D011954:Receptors, Dopamine; D004298:Dopamine