Preliminary ligand binding data for subtypes of the delta opioid receptor in rat brain membranes.
Delta opioid binding sites were assayed using [3H][D-ala2,D-leu5]enkephalin and rat brain membranes depleted of mu binding sites with the site-directed acylating agent, 2-(p-ethoxybenzyl)-1-diethylaminoethyl-5-isothiocyanatobenzimid a zole-HCI. [D-Pen2,D-Pen5]enkephalin (DPDPE), [D-Pen2,L-Pen5]enkephalin, [D-Ala2]deltorphin-I and [D-Ala2]deltorphin-II inhibition curves were characterized by slope factors (Hill coefficients) less than 1. The low slope factor of DPDPE persisted in the presence of 50 microM 5'-guanylyimidodiphosphate in the assay Quantitative analysis of [D-ala2,D-leu5]enkephalin, DPDPE and [D-Ala2]deltorphin-I binding surfaces resolved two binding sites. Whereas [D-ala2,D-leu5]enkephalin had equal affinity for both sites, DPDPE and [D-Ala2]deltorphin-I had high affinity for the high capacity binding site, and low affinity for the low capacity binding site. These data support pharmacological studies demonstrating delta receptor subtypes which mediate antinociception.
Laboratory of Medicinal Chemistry, NIDDK, NIH, Bethesda, MD 20892.
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D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D016308:Enkephalin, Leucine-2-Alanine / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011957:Receptors, Opioid / Q000378:metabolism*; D017465:Receptors, Opioid, delta; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism
D004745:Enkephalins; D009842:Oligopeptides; D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; C060208:deltorphin I, Ala(2)-; C060209:deltorphin II, Ala(2)-; D013004:Somatostatin; D016308:Enkephalin, Leucine-2-Alanine; D020881:Enkephalin, D-Penicillamine (2,5)-