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 cloparnine are transduced by two classes of receptors (D-1- and D-2-like) that belong to the superfamily of G protein-coupled receptors. In genetic hypertension, the D-1 receptor, a member of the D-1-like receptor family, is uncoupled from its G protein complex, resulting in a decreased ability to regulate renal sodium transport. The impaired D-1 receptor/G protein coupling in renal proximal tubules in genetic hypertension is secondary to abnormal phosphorylation and desensitization of the D-1 receptor caused by activating single nucleotide polymorphisms of a G protein-coupled receptor kinase, GRK type 4.