Opioid peptide receptor studies. 9. Identification of a novel non-mu- non-delta-like opioid peptide binding site in rat brain.
Quantitative binding studies resolved two high-affinity [3H][D-Ala2,D-Leu5]enkephalin binding sites in rat brain membranes depleted of mu binding sites by pretreatment with the irreversible agent BIT. The two binding sites had lower (delta ncx-2, Ki = 96.6 nM) and higher (delta ncx-1, Ki = 1.55 nM) affinity for DPDPE. The ligand-selectivity profile of the delta ncx-1 site was that of a classic delta binding site. The ligand-selectivity profile of the delta ncx-2 site was neither mu- or delta-like. The Ki values of selected agents for the delta ncx-2 site were: [pCl]DPDPE (3.9 nM), DPLPE (140 nM), and DAMGO (2.6 nM). Under these assay conditions, [3H][D-Ala2,D-Leu5]enkephalin binding to the cells expressing the cloned mu receptor is very low and pretreatment of cell membranes with BIT almost completely inhibits [3H]DAMGO and [3H][D-Ala2,D-Leu5]enkephalin binding. Intracerebroventricular administration of antisense DNA to the cloned delta receptor selectively decreased [3H][D-Ala2,D-Leu5]enkephalin binding to the delta ncx-1 site. Administration of buprenorphine to rats 24 h prior to preparation of membranes differentially affected mu, delta ncx-1, and delta ncx-2 binding sites. Viewed collectively, these studies have identified a novel non-mu- non-delta-like binding site in rat brain.
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Clinical Psychopharmacology Section, DIR, NIDA, NIH, Baltimore, MD 21224, USA.
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Partilla
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Rice
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Matecka
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Calderon
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Porreca
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Lai
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Schmidhammer
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Krassnig
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Rothman
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D000701:Analgesics, Opioid / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002047:Buprenorphine / 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; D008024:Ligands; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017465:Receptors, Opioid, delta / Q000235:genetics / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000235:genetics / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism
D000701:Analgesics, Opioid; D004745:Enkephalins; D008024:Ligands; D016376:Oligonucleotides, Antisense; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D002047:Buprenorphine; D016308:Enkephalin, Leucine-2-Alanine; D020881:Enkephalin, D-Penicillamine (2,5)-