Interaction of opioid peptides and other drugs with multiple delta ncx binding sites in rat brain: further evidence for heterogeneity.
Recent pharmacological data strongly support the hypothesis of delta receptor subtypes as mediators of both supraspinal and spinal antinociception (delta 1 and delta 2 receptors). In vitro ligand binding data, which are fully supportive of the in vivo data, are still lacking. A previous study indicated that [3H][D-Ala2,D-Leu5]enkephalin labels two binding sites in membranes depleted of mu binding sites by pretreatment with the site-directed acylating agent, 2-(p-ethoxybenzyl)-1-diethylaminoethyl-5-isothiocyanatobenzimid azole-HCI (BIT). The main goal of the present study was to develop a ligand-selectivity profile of the two delta ncx binding sites. The data indicated that naltrindole and oxymorphindole were relatively selective for site 1 (20-fold). [D-Ser2,Thr6]Enkephalin and deltorphin-II were only 2.7-fold and 2.2-fold selective for site 1. [D-Pen2,D-Pen5]Enkephalin and deltorphin-I were 80-fold and 38-fold selective for site 2. 3-Iodo-Tyr-D-Ala-Gly-Phe-D-Leu was 52-fold selective for site 1. Morphine had moderate affinity for site 1 (Ki = 16 nM), and was about 11-fold selective for site 1. Thus, of the 10 drugs studied, only DPDPE and DELT-I were selective for site 2. Viewed collectively with other data, it is likely that the delta 1 receptor and the delta ncx binding site are synonymous.
Xu
H
H
Clinical Psychopharmacology Section, NIDA Addiction Research Center, Baltimore, MD 21224.
Partilla
J S
JS
de Costa
B R
BR
Rice
K C
KC
Rothman
R B
RB
D000215:Acylation; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004347:Drug Interactions; D004723:Endorphins / Q000494:pharmacology*; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008969:Molecular Sequence Data; D009019:Morphinans / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives*; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017465:Receptors, Opioid, delta / Q000187:drug effects* / Q000378:metabolism; D012680:Sensitivity and Specificity
D004723:Endorphins; D004745:Enkephalins; D007211:Indoles; D009019:Morphinans; D009025:Morpholines; D009292:Narcotic Antagonists; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C070418:oxymorphindole; C060208:deltorphin I, Ala(2)-; D006165:Guanylyl Imidodiphosphate; D009271:Naltrexone; D020881:Enkephalin, D-Penicillamine (2,5)-; C055382:naltrindole