['Dysfunctional dopamine neurotransmission and defective D1A receptor-G protein coupling exist in renal proximal tubules (RPT) of the spontaneously hypertensive rat (SHR).', 'To determine whether the G proteins in SHR are abnormal, preventing formation of agonist high affinity sites in SHR.', 'We examined the expression levels of the alpha-subunits of G proteins, as well as D1A receptor receptor coupling to exogenously added normal G proteins, in RPT of SHR and the normotensive Wister-Kyoto (WKY) rat.', 'In the presence of 110 mmol/l NaCl, the D1A dopamine receptor-selective agonist SKF R-38393 binds both to high- and to low-affinity sites on solubilized and reconstituted D1A receptors extracted from renal proximal tubules of normotensive Wistar-Kyoto (WKY) rats. In the spontaneously hypertensive rat (SHR), SKF R-38393 bound to a single site on the reconstituted receptor with affinity values corresponding to the low-affinity state of the receptor. Western blot analyses indicated that the alpha-subunit of the guanine nucleotide binding protein (G-protein), Gs, was expressed at similar levels, whereas G(o)alpha was not expressed in proximal tubule membranes from WKY rats and SHR. Pretreatment of proximal tubule membranes with the alkylating agent N-ethylmaleimide in the presence of SKF R-38393 inactivated alpha-subunits of endogenous G-proteins, but not D1A receptors, resulting in loss of high-affinity binding sites in WKY rats. These N-ethylmaleimide-treated D1A receptors from WKY rats, when reconstituted with exogenous sources of G-proteins, were able to couple to these exogenous G-proteins, with complete restoration of high-affinity sites. Moreover, the affinity values and the proportion of these hybrid sites were similar to those of untreated receptors, and these affinity sites were regulated by guanine nucleotide analogs. Reconstitution of D1A receptors from SHR with the same exogenous G-proteins failed to similarly induce formation of the high-affinity binding sites in the hybrid reconstituted systems, and SKF R-38393 continued to bind in a single low-affinity state of the receptor.'] Is dysfunctional D1A receptor-G-protein coupling in proximal tubules of spontaneously hypertensive rats due to abnormal G-proteins?