title: Characterization of [125I]AR-M100613, a high-affinity radioligand for delta opioid receptors.
abstract: AR-M100613 ([I]-Dmt-c[-D-Orn-2-Nal-D-Pro-D-Ala-]) is the iodinated analog of a cyclic casomorphin previously shown to be a potent antagonist at the delta opioid receptor. Specific [125I]AR-M100613 binding to rat whole brain membranes was saturable, reversible, and best fit to a one-site model (Kd = 0.080 +/- 0.008 nM, Bmax = 45.2 +/- 4.4 fmol/mg protein). [125I]AR-M100613 binding was displaced with high affinity by the delta opioid receptor ligands SNC-80, Deltorphin II and DPDPE but not the mu or kappa-selective receptor ligands DAMGO and U69593. Residual non-selective binding of [125I]AR-M 100613 to mu opioid receptors is blocked by the addition of CTOP to the assay buffer. [35S]GTPgammaS binding assays indicate that AR-M100613 is a potent, selective, and reversible antagonist for delta opioid receptors in rat brain membranes. The high-affinity, high specific activity, low nonspecific binding and antagonist profile of [125I]AR-M100613 favor its use as a radiochemical probe for delta opioid receptors.
authors.affiliation: AstraZeneca R & D Montreal, St-Laurent, Quebec, Canada.
authors.forename: G L
authors.initials: GL
authors.lastname: Fraser
authors.forename: M
authors.initials: M
authors.lastname: Labarre
authors.forename: C
authors.initials: C
authors.lastname: Godbout
authors.forename: J
authors.initials: J
authors.lastname: Butterworth
authors.forename: P B
authors.initials: PB
authors.lastname: Clarke
authors.forename: K
authors.initials: K
authors.lastname: Payza
authors.forename: R
authors.initials: R
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D007457:Iodine Radioisotopes; D007700:Kinetics; D008024:Ligands; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000378:metabolism*
chemical_list: D007457:Iodine Radioisotopes; D008024:Ligands; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C060209:deltorphin II, Ala(2)-; D009271:Naltrexone; C055382:naltrindole