Characterization of Specific Opioid Binding Sites in Neural Membranes from the Myenteric Plexus of Porcine Small Intestine

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δ- and κ-Opioid receptors (OPRs), but not μ-OPRs, are expressed in the myenteric plexus of the porcine distal small intestine. In a subpopulation of myenteric neurons, δ- and κ-OPRs seem to be colocalized and may functionally interact. In this study, radioligand binding was used to characterize myenteric OPR populations in detail. The nonselective OPR antagonist [3H]diprenorphine bound to a single, high-affinity site in myenteric neural membrane homogenates. Naloxone displaced 65 and 59% of [3H]diprenorphine binding from this site in Na+-free Tris and Krebs-HEPES buffers, respectively. Naltrexone-derived δ- and κ-OPR antagonists, including naltriben, 7-benzylidenenaltrexone, nor-binaltorphimine, and 5′-guanidinonaltrindole, displaced [ 3H]diprenorphine from two distinct binding sites to levels similar to that of naloxone. The selective δ-OPR ligands Tyr-1,2,3,4-tetrahydroisoquinoline-Phe-Phe-OH (TIPP), [D-Pen 2,D-Pen5]enkephalin (DPDPE), [D-Ala2, Glu 4]deltorphin II, and (+)-4-[(αR)-α ((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl-3-methoxybenzyl)-N, N-diethylbenzamide (SNC-80) and the κ-OPR agonist (D-(5α,7α ,8β)-(-)-N-methyl-N-(7-(1-pyrrolidinyl)-1-oxoaspiro-(4,5)dec-8-yl) benzeneacetamide (U-69,593) displaced [3H]diprenorphine from three independent binding sites; these included high-affinity δ- and κ-OPR sites, and a residual binding site. Residual [ 3H]diprenorphine binding was displaced by the selective κ-OPR antagonist nor-binaltorphimine after saturation of δ and κ sites, respectively, with DPDPE and U-69,593. The residual binding site displayed low affinity for δ- and κ-OPR agonists and TIPP, as well as moderate affinity for naltrexone-derived ligands, properties reminiscent of δ-/κ-OPR heterodimers.

Original languageEnglish (US)
Pages (from-to)385-393
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Issue number1
StatePublished - Jan 2004


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