ALTERATION OF ASSOCIATION OF AGONIST-ACTIVATED RENAL D1(A) DOPAMINE-RECEPTORS WITH G-PROTEINS IN PROXIMAL TUBULES OF THE SPONTANEOUSLY HYPERTENSIVE RAT

Background Defective D1(A) dopamine receptor-G protein coupling has be en identified in renal proximal tubules of the spontaneously hypertens ive rat (SHR). Objective To determine whether association of D1(A) dop amine receptors with the alpha subunits of G proteins in kidney of SHR is normal. Methods We analyzed the association of agonist-activated [ I-125]-labeled D1(A) dopamine receptors in kidneys of SHR and the norm otensive Wistar-Kyoto (WKY) rat through immunoprecipitation, using hig hly specific antipeptide antibodies directed against or subunits of G proteins. Results We have shown for the first time that the D1(A) rece ptors of renal proximal tubules are associated with the adenylyl cycla se inhibitory G proteins G(i)alpha. The association of WKY rat proxima l tubule D1(A) receptors with G(i1)alpha and G(i2)alpha in the presenc e of agonist is significantly (P < 0.01) greater (2.4-fold and 3.1-fol d greater, respectively) than it is without agonist. D1(A) receptors o f WKY rat also exhibit (twofold greater) association with G(s)alpha, c onsistently with the ability of these receptors to mediate stimulation of adenylyl cyclase. The WKY rat D1(A) receptors do not associate eit her with G(i1)alpha or with G(i2)alpha. The D1(A) receptors of SHR pro ximal tubule membranes appear to be resistant to activation by agonist and do not associate with G(o)alpha G(q)alpha and any of the subunits of G(i)alpha. However, the SHR D1(A) sites exhibit a modestly (1.7-fo ld) greater association with G(q)alpha, which was not statistically si gnificant. The differences among associations of the D1(A) receptors o f WKY rat and SHR with these G alpha proteins may be important in unde rstanding renal dopaminergic functions in normal and pathophysiologic states. J Hypertens 16:1307-1313 (C) 1998 Lippincott Williams & Wilkin s.