Dopamine receptor-coupling defect in hypertension.
Dopamine synthesized in non-neural tissues, eg, renal proximal tubule, functions in an autocrine or paracrine manner. The effects of dopamine are transduced by two classes of receptors (D1- and D2-like) that belong to the superfamily of G protein-coupled receptors. In genetic hypertension, the D1 receptor, a member of the D1-like receptor family, is uncoupled from its G protein complex, resulting in a decreased ability to regulate renal sodium transport. The impaired D1 receptor/G protein coupling in renal proximal tubules in genetic hypertension is secondary to abnormal phosphorylation and desensitization of the D1 receptor caused by activating single nucleotide polymorphisms of a G protein-coupled receptor kinase, GRK type 4.
Jose
Pedro A
PA
Georgetown University Medical Center, 3800 Reservoir Road, NW, Washington, DC 20007, USA. pjose01@georgetown.edu
Eisner
Gilbert M
GM
Felder
Robin A
RA
D000818:Animals; D054771:G-Protein-Coupled Receptor Kinase 4; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics
D020710:RGS Proteins; D011954:Receptors, Dopamine; D017346:Protein Serine-Threonine Kinases; D054771:G-Protein-Coupled Receptor Kinase 4; C517855:GRK4 protein, human; D019204:GTP-Binding Proteins