title: Characterization and distribution of [3H]ohmefentanyl binding sites in the human brain.
abstract: Binding properties and localization of [3H]ohmefentanyl, a new ligand for mu opioid receptors, were investigated on normal human brain sections. Binding assays performed at the level of the basal ganglia revealed: (1) a steady-state binding reached after 60 min incubation at room temperature, (2) the presence, in saturation experiments, of an apparent single class of binding sites with a Kd = 1.68 +/- 0.45 nM and a Bmax = 162 +/- 9 fmol/mg protein, (3) an order of potency to inhibit [3H]ohmefentanyl binding as follows: ohmefentanyl greater than [D-Ala2, MePhe4, Gly-ol5] enkephalin (DAGO) greater than ethylketocyclazocine (EKC) much greater than Tyr-D-Ser(OtBu)-Gly-Phe-Leu-Thr(OtBu) (BUBU) and U-50,488H. Quantitative autoradiography showed an heterogeneous distribution of [3H]ohmefentanyl binding sites with the highest densities in amygdala, medical geniculate body, thalamus, and caudate nucleus. Binding characteristics and anatomical distribution also show that [3H]ohmefentanyl may bind to a small proportion of additional sites called "DAGO-inaccessible [3H]ohmefentanyl specific binding sites." [3H]Ohmefentanyl binding to these sites can be partly inhibited by sigma ligands such as 1,3-di-o-tolylguanidine (DTG) and haloperidol. However, unlabeled DAGO inhibited more than 80% of [3H]ohmefentanyl specific binding in most of the human brain regions studied, suggesting that the major population of sites labeled by [3H]ohmefentanyl represented mu opioid receptors.
authors.affiliation: INSERM U.339, Centre de Recherches Saint-Antoine, Paris, France.
authors.forename: H
authors.initials: H
authors.lastname: Wang
authors.forename: A
authors.initials: A
authors.lastname: Sarrieau
authors.forename: D
authors.initials: D
authors.lastname: Pélaprat
authors.forename: B P
authors.initials: BP
authors.lastname: Roques
authors.forename: A
authors.initials: A
authors.lastname: Vanhove
authors.forename: N
authors.initials: N
authors.lastname: Kopp
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Chi
authors.forename: W
authors.initials: W
authors.lastname: Rostène
mesh_terms: D000328:Adult; D000368:Aged; D001345:Autoradiography; D001479:Basal Ganglia / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry; D004723:Endorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics
chemical_list: D004723:Endorphins; D004745:Enkephalins; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C037016:F 7302; D005283:Fentanyl