Alteration of association of agonist-activated renal D1A dopamine receptors with G proteins in proximal tubules of the spontaneously hypertensive rat


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Abstract

BackgroundDefective D1A dopamine receptor-G protein coupling has been identified in renal proximal tubules of the spontaneously hypertensive rat (SHR).ObjectiveTo determine whether association of D1A dopamine receptors with the α subunits of G proteins in kidney of SHR is normal.MethodsWe analyzed the association of agonist activated [125I]-labeled D1A dopamine receptors in kidneys of SHR and the normotensive Wistar-Kyoto (WKY) rat through immunoprecipitation, using highly specific antipeptide antibodies directed against α subunits of G proteins.ResultsWe have shown for the first time that the D1A receptors of renal proximal tubules are associated with the adenylyl cyclase inhibitory G proteins Giα. The association of WKY rat proximal tubule D1A receptors with Gi1α and Gi2α in the presence of agonist is significantly (P < 0.01) greater (2.4-fold and 3.1-fold greater, respectively) than it is without agonist. D1A receptors of WKY rat also exhibit (twofold greater) association with Gsα, consistently with the ability of these receptors to mediate stimulation of adenylyl cyclase. The WKY rat D1A receptors do not associate either with Goα or with Gqα. The D1A receptors of SHR proximal tubule membranes appear to be resistant to activation by agonist and do not associate with Gsα, Goα and any of the subunits of Giα. However, the SHR D1A sites exhibit a modestly (1.7-fold) greater association with Gqa, which was not statistically significant. The differences among associations of the D1A receptors of WKY rat and SHR with these Ga proteins may be important in understanding renal dopaminergic functions in normal and pathophysiologic states.

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