Affinity Labels for Opioid Receptors

Takemori, A. E.; Portoghese, Philip S.

doi:10.1146/annurev.pa.25.040185.001205

Cited by 103 publications

(59 citation statements)

References 78 publications

(98 reference statements)

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“…To further test this hypothesis, the selective opioid antagonists were employed. In mammals these highly selective μ, κ and δ antagonists affect the binding of opioid agonists only at their respective receptors [38,39]. As mentioned above, behavioral studies revealed a lack of selectivity of these antagonists in Rana pipiens and binding studies with [ 3 H]-naloxone in brain yielded nearly identical K i values for the selective antagonists [19,34].…”

Section: Competition Binding With Highly-selective Opioid Antagonistsmentioning

confidence: 88%

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Selective opioid agonist and antagonist competition for [3H]-naloxone binding in amphibian spinal cord

2000

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Opioids elicit antinociception in mammals through three distinct types of receptors designated as μ, κ and δ. However, it is not clear what type of opioid receptor mediates antinociception in nonmammalian vertebrates. Radioligand binding techniques were employed to characterize the site(s) of opioid action in the amphibian, Rana pipiens. Naloxone is a general opioid antagonist that has not been characterized in Rana pipiens. Using the non-selective opioid antagonist, [ 3 H]-naloxone, opioid binding sites were characterized in amphibian spinal cord. Competitive binding assays were done using selective opioid agonists and highly-selective opioid antagonists. Naloxone bound to a single-site with an affinity of 11.3 nM and 18.7 nM for kinetic and saturation studies, respectively. A B max value of 2725 fmol/mg protein in spinal cord was observed. The competition constants (K i ) of unlabeled μ, κ and δ ranged from 2.58 nM to 84 μM. The highly-selective opioid antagonists yielded similar K i values ranging from 5.37 to 31.1 nM. These studies are the first to examine opioid binding in amphibian spinal cord. In conjunction with previous behavioral data, these results suggest that non-mammalian vertebrates express a unique opioid receptor which mediates the action of selective μ, κ and δ opioid agonists.

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Section: Competition Binding With Highly-selective Opioid Antagonistsmentioning

confidence: 88%

“…A number of μ-, κ-and δ-selective opioid agonists were used to compete with naloxone binding. Finally, the highly-selective μ opioid antagonist, β-FNA [38], the δ-selective antagonist, NTI [25] and the κ-selective antagonist, nor-BNI [39], were assayed against naloxone binding.…”

Section: Introductionmentioning

confidence: 99%

Selective opioid agonist and antagonist competition for [3H]-naloxone binding in amphibian spinal cord

2000

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“…Furthermore, highly specific antagonists for the µ-opioid receptor (funaltrexamine [85] [86]); for the δ-receptor (naloxonazine; [87]) and the KOR1 receptor (nor-binaltorphimine (4; Nor-BNI) [88]) were used. Autoradiographic analysis confirmed that the most frequent types of opioid receptors in the dorsal horn of the spinal cord are µ and κ receptors (with some species differences) while in the brain special regions achieved large densities of µ, δ, or κ receptors [82]- [84].…”

Section: Opioid Receptor Ligandsmentioning

confidence: 99%

Neuropeptide Receptors in Pain Circuitries: Useful Targets for CNS Imaging with Non-Peptide Ligands Suitable for PET?

Pissarek¹

2014

WJNS

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“…Site-directed electrophilic affinity ligands have been utilized with much success as tools for characterization of opioid receptors [1]. Efforts in our laboratory led to the synthesis and use of the isothiocyanate-derived irreversible ligands BIT [2], FIT [2] and SUPERFIT [3] for the characterization of/z-and 5-0pioid receptors.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, ICV injection of the less reactive/5'-funaltrexamine (6'-FNA) [5] into rats resulted in a selective wash-resistant inhibition of /z-receptor binding [6]. Compounds which selectively deplete opioid receptor subtypes in vivo can allow one to perform direct observation of the physiological effects associated with these receptor types [1].…”

Section: Introductionmentioning

confidence: 99%

Synthesis of an affinity ligand (‘UPHIT’) for in vivo acylation of the κ‐opioid receptor

et al. 1989

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zeneacetamide, 3a) of the highly selective x-opioid receptor agonist, U50,488, was prepared as a potential site-directed affinity ligand for acylation of ~c-opioid receptors in vivo. The isothiocyanate (3a) which we have designated UPHIT and its enantiomer (3b) were synthesized in 3 steps starting from optically pure (1S,2S)-(+)-trans-2-pyrrolidinyl-N-methylcyclohexylamine (4a) and its enantiomer (4b), respectively, thus defining their absolute stereochemistry. Binding in vitro of the IS,2S enantiomer 3a to x receptors labelled by pH]U69,593 was shown to occur with an ICs0 value of 25.92 ___ 0.36 nM, whereas 827.42 _ 5.88 and 115.10 + 1.23 nM were obtained for the ICso value of the IR,2R enantiomer (3b) and ( + )-3 respectively. Intracerebroventricular (ICV) injection of 100/zg of (_+)-3 into guinea-pig brain followed by analysis of remaining x-binding sites 24 h later revealed that (+)-3 depleted 98% of the x receptors that bind [3H]U69,593 and 40% of those that bind [aH]bremazocine. These preliminary data suggest exciting uses for these compounds in furthering our knowledge of the x-opioid receptor.

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Affinity Labels for Opioid Receptors

Cited by 103 publications

References 78 publications

Selective opioid agonist and antagonist competition for [3H]-naloxone binding in amphibian spinal cord

Selective opioid agonist and antagonist competition for [3H]-naloxone binding in amphibian spinal cord

Neuropeptide Receptors in Pain Circuitries: Useful Targets for CNS Imaging with Non-Peptide Ligands Suitable for PET?

Synthesis of an affinity ligand (‘UPHIT’) for in vivo acylation of the κ‐opioid receptor

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