title: [3H]U69,593 binding in guinea-pig brain: comparison with [3H]ethylketazocine binding at the kappa-opioid sites.
abstract: [3H]U69,593 and [3H]ethylketazocine (mu + delta suppressed) binding was measured in homogenates of guinea-pig brain. Both ligands bind with high affinity to a single class of opioid sites. The relative equilibrium dissociation constant (KD) for [3H]U69,593 is 1.15 nM, while [3H]ethylketazocine has a KD value of 0.33 nM. Their respective maximum binding capacities are 4.49 and 4.48 pmol/g of wet tissue. Various mu-selective, delta-selective, kappa-selective, and nonselective opioids were tested in competition studies against the binding of [3H]U69,593 or [3H]ethylketazocine (in the presence of mu- and delta-blockers) to measure their relative affinity. [D-Ala2, MePhe4,Gly5-ol]enkephalin (mu-selective) has low affinity (600-3000 nM) and [D-Pen2,D-Pen5]enkephalin and [D-Ser2, Leu5, Thr6]enkephalin (delta-selective) have very low affinities (greater than 20,000 nM) at the sites labelled with [3H]U69,593 or [3H]ethylketazocine. On the other hand, unlabelled U69,593, U50,488H, and tifluadom (all three kappa-selective substances) display high affinity (1-5 nM) at those sites. Nonselective opioids, such as bremazocine, levorphanol, and ethylketazocine show similar affinities at the sites labelled with [3H]U69,593 and at the sites labelled with [3H]ethylketazocine. These data indicate that [3H]U69,593 is a selective high-affinity ligand for the same sites that are labelled with [3H]ethylketazocine (in the presence of mu- and delta-blockers) and that these are kappa-sites.
authors.affiliation: Département de pharmacologie, Université de Montréal, Québec, Canada.
authors.forename: M
authors.initials: M
authors.lastname: Tiberi
authors.forename: P
authors.initials: P
authors.lastname: Payette
authors.forename: R
authors.initials: R
authors.lastname: Mongeau
authors.forename: J
authors.initials: J
authors.lastname: Magnan
mesh_terms: D044482:Benzeneacetamides; D001921:Brain / Q000378:metabolism*; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000378:metabolism; D016314:Ethylketocyclazocine; D007700:Kinetics; D011759:Pyrrolidines / Q000378:metabolism*; D011869:Radioligand Assay; D011957:Receptors, Opioid / Q000378:metabolism*
chemical_list: D044482:Benzeneacetamides; D011759:Pyrrolidines; D011957:Receptors, Opioid; D016314:Ethylketocyclazocine; C045444:U 69593; D003496:Cyclazocine