Selective labeling of κ 2 opioid receptors in rat brain by [125I]IOXY: Interaction of opioid peptides and other drugs with multiple κ 2a binding sites

@article{Ni1993SelectiveLO,
  title={Selective labeling of $\kappa$
 2 opioid receptors in rat brain by [125I]IOXY: Interaction of opioid peptides and other drugs with multiple $\kappa$
 2a binding sites},
  author={Q. Ni and Heng Xu and J. Partilla and B. Costa and K. Rice and R. Rothman},
  journal={Peptides},
  year={1993},
  volume={14},
  pages={1279-1293}
}
Recent studies from our laboratory resolved two subtypes of the kappa 2 binding site, termed kappa 2a and kappa 2b, using guinea pig, rat, and human brain membranes depleted of mu and delta receptors by pretreatment with the site-directed acylating agents BIT (mu-selective) and FIT (delta-selective). 6 beta-Iodo-3,14-dihydroxy-17-cyclopropylmethyl-4,5 alpha-epoxymorphinan (IOXY), an opioid antagonist that has high affinity for kappa 2 sites, was radioiodinated to maximum specific activity (2200… Expand
Opioid peptide receptor studies. 3. Interaction of opioid peptides and other drugs with four subtypes of the κ 2 receptor in guinea pig brain
TLDR
The results indicated that [125I]IOXY, like [3H]bremazocine, selectively labels kappa 2 binding sites in rat brain membranes pretreated with BIT and FIT. Expand
Opioid peptide receptor studies. 9. Identification of a novel non-μ- non-δ-like opioid peptide binding site in rat brain
Abstract The two binding sites had lower (δ ncx-2 , Ki = 96.6 nM) and higher (δ ncx-1 , Ki = 1.55 nM) affinity for DPDPE. The ligand-selectivity profile of the δ ncx-1 site was that of a classic δExpand
[125I]IOXY-AGO: A high affinity, mu-selective agonist opioid receptor ligand
Abstract We previously reported that epimeric 6β-iodo-3,14-dihydroxy-17-cyclopropylmethyl-4,5α-epoxymorphinan (IOXY) was a potent opioid receptor antagonist with high affinity μ, κ 1 and κ 2 bindingExpand
6β‐[125Iodo]‐3, 14‐dihydroxy‐17‐methyl‐4, 5α‐epoxymorphinan ([125I]IOXY‐AGO): A potent and selective radioligand for opioid μ receptors
TLDR
The present study synthesized the agonist congener of IOXY, 6β‐iodo‐3,14‐dihydroxy‐17‐cyclopropylmethyl‐4,5α‐epoxymorphinan, and named this novel agent IOXY‐AGO for IO XY‐agonist, suggesting that [125I]IOXY‐ AGO will be a useful radioligand for characterizing opioid μ receptors. Expand
SoRI 9409, a non-peptide opioid μ receptor agonist/δ receptor antagonist, fails to stimulate [35S]-GTP-γ-S binding at cloned opioid receptors
Abstract Recent work suggests that opioids which combine μ agonist and δ antagonist activity may be non-addicting antinociceptive agents. SoRI 9409Expand
Opioid peptide receptor studies. 10. Nor‐BNI differentially inhibits kappa receptor agonist‐induced G‐protein activation in the guinea pig caudate: Further evidence of kappa receptor heterogeneity
TLDR
Results suggest that (+)‐tifluadom and U69,593 activate pharmacologically different receptors, and functional evidence in support of kappa receptor heterogeneity is provided. Expand
Opioid peptide receptor studies. 14. Stereochemistry determines agonist efficacy and intrinsic efficacy in the [35S]GTP‐γ‐S functional binding assay
TLDR
Replacement of the methyl group with the phenethyl group on the piperidine nitrogen of NIH8508 and NIH8509 increased affinity for the μ receptor and eliminated any agonist effect, supporting the hypothesis that certain structural features make these compounds antagonists. Expand
κ2 Opioid Receptors in Limbic Areas of the Human Brain Are Upregulated by Cocaine in Fatal Overdose Victims
TLDR
Findings demonstrate for the first time that κ2 receptor numbers are upregulated by cocaine exposure and may play a role in the motivational incentive associated with episodes of binge cocaine use and in the dysphoria that follows abrupt cocaine withdrawal. Expand
Opioid peptide receptor studies. 4. Antisense oligodeoxynucleotide to the delta opioid receptor delineates opioid receptor subtypes
TLDR
It is demonstrated that delta antisense DNA selectively affects the delta ncx-2 site sparing the other putative delta receptor subtypes and kappa 2 receptor sub types, suggesting a powerful approach to distinguishing between postulated receptor subtype subtypes. Expand
Dihydrocodeinone-hydrazone, dihydrocodeinone-oxime, naloxone-3-ome-oxime, and clocinnamox fail to irreversibly inhibit opioid kappa receptor binding
TLDR
The hypothesis that certain dihydrocodeinone and oxicodone derivatives, which have been shown to irreversibly block low affinity [3H]naloxone binding sites, would also bind irreversible to opioid kappa receptor subtypes is tested. Expand
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TLDR
Quantitative autoradiographic studies demonstrated that kappa 2a and kapp 2b binding sites are heterogeneously distributed in guinea pig brain, and that the anatomical distribution of kappa 1 binding sites reported in the literature is different from that observed in this study for the kappa2 binding sites. Expand
Interaction of opioid peptides and other drugs with multiple kappa receptors in rat and human brain. Evidence for species differences
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Quantitative examination of [3H]bremazocine binding resolved two kappa 2 binding sites in both rat and human brain whose ligand selectivity patterns differed from that of the guinea pig, suggesting that there may be considerable variation in the ligand recognition site of kappa receptor subtypes among mammalian species. Expand
Preparation of rat brain membranes highly enriched with opiate kappa binding sites using site-directed acylating agents: Optimization of assay conditions
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These and additional data suggest that the binding of [3H]bremazocine to the kappa binding site of rat brain is optimally assayed at 0 degrees C in the presence of 0.4 M NaCl using BIT/FIT-treated membranes and thatRat brain is endowed with a high level of kappabinding sites. Expand
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The [3H]EKC site has opiate receptor characteristics and appears to be the most abundant opiates receptor in rat brain, but its binding selectivity profile is not that of a kappa receptor and has the pharmacological properties that correspond to those of the beta-endorphin-specific, epsilon receptor that has been hypothesized to exist for some time. Expand
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TLDR
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TLDR
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