Vanadate inhibits agonist binding to D2 dopamine receptor.
Orthovanadate (in the micromolar range) inhibits the high-affinity binding of the D2 dopamine receptor to specific agonists (apomorphine and N-propylnorapomorphine), while it does not affect the binding to D2 antagonists (spiperone and haloperidol). These effects of vanadate resemble those observed with guanine nucleotides or their analogs. However, in contrast to the guanine nucleotides, vanadate does not induce dissociation of the D2 dopamine receptor from its related G proteins, suggesting that vanadate and guanine nucleotides may exert their effect on the D2 dopamine receptor via different mechanisms. The effect of vanadate on agonist binding was shown to be ATP dependent and correlated with increased protein phosphorylation.
Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Z
Z
Elazar
S
S
Fuchs
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000378:metabolism; D001667:Binding, Competitive; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D006220:Haloperidol / Q000378:metabolism; D007700:Kinetics; D011954:Receptors, Dopamine / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2; D013134:Spiperone / Q000378:metabolism; D014638:Vanadates / Q000494:pharmacology*
D015259:Dopamine Agents; D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D014638:Vanadates; D013134:Spiperone; C009074:N-n-propylnorapomorphine; D006220:Haloperidol; D001058:Apomorphine