Comparative properties of SH-groups at mu, delta and kappa opioid receptor.
Crude synaptosomal membrane from rat brain was treated with three kinds of DTNB analogs. The receptor bindings of opioids were inhibited on a concentration dependent manner by 5-nitro-2-PDS and DTNHEB, regardless of the receptor types. DTNB showed complete inhibition of the bindings of mu and delta agonists. But, the effect of DTNB on the binding of kappa agonist was incomplete, resulting in approximately 50% inhibition at the maximal effective concentration. Treating the membrane with DTNB, but not with DTNHEB and 5-nitro-2-PDS, completely eliminated inhibitory effects of guanine nucleotides on agonist binding. These results suggest that one SH-group, being sensitive to DTNHEB, exists at an active center of the receptor binding site(R) and another SH-group, blocked by DTNB, forms a binding site for GTP in GTP-binding protein(Ni), and that a coupling mechanism between R and Ni at kappa receptor differs from those at mu and delta receptor.
Nozaki
M
M
Dept. of Pharmacology, Gifu Univ. Sch. of Med., Japan.
Niwa
M
M
Fujimura
H
H
D000818:Animals; D001921:Brain / Q000378:metabolism*; D004228:Dithionitrobenzoic Acid / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D007700:Kinetics; D051381:Rats; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013439:Sulfhydryl Reagents / Q000494:pharmacology*; D013574:Synaptosomes / Q000378:metabolism*
D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D013438:Sulfhydryl Compounds; D013439:Sulfhydryl Reagents; D004228:Dithionitrobenzoic Acid