Evidence for the coupling of Gq protein to D1-like dopamine sites in rat striatum: possible role in dopamine-mediated inositol phosphate formation.
The role of G proteins in mediating the coupling of D1 dopamine receptors to inositol phosphate formation was investigated in rat brain striatum. Pertussis toxin-activated ADP-ribosylation ( > or = 95%) did not affect the ability of the D1 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 D1 agonist SKF38393 and blocked by the D1 antagonist SCH23390. In contrast, the D2/3 dopamine receptor agonist quinpirole stimulated guanine nucleotide binding to G alpha i, and dopamine-stimulated activation of G alpha i was attenuated by the D2 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 D1-like binding sites labeled with [3H]SCH23390. The D1-like receptors that coprecipitated with G alpha s-but not with G alpha q can be recognized by a specific D1 dopamine receptor antibody. The data provide evidence to suggest that in addition to coupling to Gs/adenylyl cyclase, D1-like dopamine sites that couple to Gq may mediate dopamine-stimulated formation of inositol phosphates in the rat striatum.
Wang
H Y
HY
Department of Pharmacology, Medical College of Pennsylvania, Philadelphia 19129, USA.
Undie
A S
AS
Friedman
E
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D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D003342:Corpus Striatum / Q000737:chemistry* / Q000187:drug effects / Q000648:ultrastructure; D004298:Dopamine / Q000494:pharmacology / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism* / Q000502:physiology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000096:biosynthesis*; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D037342:Pertussis Toxin; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D018491:Dopamine Agonists; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D017447:Receptors, Dopamine D1; D013462:Sulfur Radioisotopes; D010566:Virulence Factors, Bordetella; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000244:Adenosine Diphosphate; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D006160:Guanosine Triphosphate; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D004298:Dopamine