D2 dopamine receptor-G protein coupling. Cross-regulation of agonist and guanosine nucleotide binding sites.
The cross regulation of agonist binding to D2 dopamine receptors and guanosine nucleotide binding to G proteins was studied using membranes of Chinese hamster ovary cells expressing rat D2short dopamine receptors. All guanosine nucleotides studied caused a concentration-dependent loss of high-affinity agonist binding sites of D2 receptors with potencies corresponding to their affinity to bind to G proteins in these membranes. On the other hand, the dopaminergic agonists, but not antagonists, decreased the affinities of guanosine diphosphate and guanosine monophosphate, but not of guanosine 5'-(gamma-thiotriphosphate). The cross regulation of ligand binding to D2 dopamine receptors and G proteins suggests the existence of several conformational states of these proteins during the signal transduction and that the high-affinity state of agonist binding is a transient state of the agonist-receptor-G protein complex, where no nucleotides are bound.
Institute of Chemical Physics, University of Tartu, Jakobi Street 2, EE-51 014, Tartu, Estonia. ago@ut.ee
A
A
Rinken
A
A
Terasmaa
G
G
Raidaru
K
K
Fuxe
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004298:Dopamine / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000031:analogs & derivatives / Q000378:metabolism*; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000378:metabolism*; D006157:Guanosine Monophosphate / Q000378:metabolism*; D020891:Raclopride / Q000378:metabolism; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013873:Thionucleotides / Q000378:metabolism*
D017448:Receptors, Dopamine D2; D013873:Thionucleotides; C034883:guanosine 5'-O-(2-thiotriphosphate); D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D020891:Raclopride; C023427:guanosine 5'-O-(2-thiodiphosphate); D006157:Guanosine Monophosphate; D019204:GTP-Binding Proteins; D004298:Dopamine