Dependence of the coupling of dopamine receptors to G proteins on the protein redox state in the neural plasma membranes of pond snail.
Binding analysis using [3H]dopamine has shown that reduction of protein thiol groups with dithiothreitol (DTT) led to a dual effect on the receptors. First, the amount of dopamine-binding sites on the membranes and their affinity to the ligand were decreased. Second, the affinity of the receptors to [3H]dopamine was enhanced in the presence of GDP. Binding of D(1) antagonist [3H]SCH23390 to dopamine receptors increased following DTT treatment, opposite to the case with D(1) agonist [3H]SKF38393. The displacement of [3H]GDP by GTPgammaS was depressed by dopamine. Stimulation of [3H]GDP binding by dopamine was potentiated after incubation with DTT. Membrane nitrosylation eliminated the reciprocal dependence of GDP and dopamine binding to the membranes. It is suggested that binding of dopamine to the receptors can lead to both stimulation and inhibition of G protein activity, and the ratio of these effects depends on the reduction and oxidation of sulfhydryl groups of membrane proteins. Thiol reduction potentiated inhibitory action of dopamine receptors on coupled G proteins, and nitrosylation led to their uncoupling.
Prudnikov
Igor M
IM
Department of Neurochemistry, A.A. Bogomoletz Institute of Physiology, Bogomoletz Street 4, 01024 Kiev, Ukraine. malysh@serv.biph.kiev.ua
Tsyvkin
Vladimir N
VN
D000818:Animals; D001665:Binding Sites; D001923:Brain Chemistry; D002462:Cell Membrane / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010084:Oxidation-Reduction; D011954:Receptors, Dopamine / Q000737:chemistry / Q000378:metabolism*; D012908:Snails / Q000166:cytology / Q000378:metabolism*
D008024:Ligands; D011954:Receptors, Dopamine; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D020962:Heterotrimeric GTP-Binding Proteins; D004298:Dopamine