Evidence for the coupling of Gq protein to D1-like dopamine sites in rat striatum: possible role in dopamine-mediated inositol phosphate formation
Wang, H.Y.; Undie, A.S.; Friedman, E.
Molecular Pharmacology 48(6): 988-994
1995
ISSN/ISBN: 0026-895X PMID: 8848015 Document Number: 443105
The role of G proteins in mediating the coupling of D-1 dopamine receptors to inositol phosphate formation was investigated in rat brain striatum. Pertussis toxin-activated ADP-ribosylation ( gtoreq 95%) did not affect the ability of the D-1 agonist SKF38393 to stimulate the generation of inositol phosphates in striatal slices. Stimulation of striatal membranes with dopamine in the presence of (35S)GTP-gamma-S or (alpha-32P)GTP increased guanine nucleotide binding to G-alpha-s, G-alpha-i, and G-alpha-q in a concentration-dependent fashion. The activation of G-alpha-s and G-alpha-q was mimicked by the D-1 agonist SKF38393 and blocked by the D-1 antagonist SCH23390. In contrast, the D-2/3 dopamine receptor agonist quinpirole stimulated guanine nucleotide binding to G-alpha-i, and dopamine-stimulated activation of G-alpha-i was attenuated by the D-2 antagonist I-sulpiride. Furthermore, antisera directed against G-alpha-s or G-alpha-q but not G-alpha-i, G-alpha-o, or G-alpha-z precipitated specific D-1-like binding sites labeled with (3H)SCH23390. The D-1-like receptors that coprecipitated with G-alpha-s- but not with G-alpha-q can be recognized by a specific D-1 dopamine receptor antibody. The data provide evidence to suggest that in addition to coupling to G-s/adenylyl cyclase, D-1-like dopamine sites that couple to G-q may mediate dopamine-stimulated formation of inositol phosphates in the rat striatum.