G(i1) and G(oA) differentially determine kinetic efficacies of agonists for kappa-opioid receptor.
We examined the diversity of single receptor function by measuring receptor-G protein coupling in the baculovirus-Sf21 expression system. In comparative studies using Sf21 cell membranes expressing kappa-opioid receptor (KOR) plus Galpha(i1)beta(1)gamma(2) or KOR plus Galpha(oA)beta(1)gamma(2), there was no significant difference between both preparations in the K(i) values of various kappa-opioid ligands for the displacement of [(3)H]U69593 binding. However, a marked difference in the rank order of agonists to stimulate [(35)S]GTPgammaS binding was observed between both preparations. These findings suggest that agonist efficacy is dependent on the population of different G proteins expressed in various tissues.
Kohno
M
M
Department of Molecular Pharmacology and Neuroscience, Nagasaki University School of Pharmaceutical Sciences, 1-14 Bunkyo-machi, Nagasaki, Japan.
Fukushima
N
N
Yoshida
A
A
Ueda
H
H
D000818:Animals; D044482:Benzeneacetamides; D001667:Binding, Competitive; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism / Q000494:pharmacology; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008024:Ligands; D008274:Magnesium / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D011759:Pyrrolidines / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018411:Spodoptera / Q000166:cytology; D013816:Thermodynamics; D014161:Transduction, Genetic
D044482:Benzeneacetamides; D008024:Ligands; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D006153:Guanosine Diphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D020962:Heterotrimeric GTP-Binding Proteins; D008274:Magnesium; C045444:U 69593