Opioid peptide receptor studies. 3. Interaction of opioid peptides and other drugs with four subtypes of the κ 2 receptor in guinea pig brain

  title={Opioid peptide receptor studies. 3. Interaction of opioid peptides and other drugs with four subtypes of the $\kappa$
 2 receptor in guinea pig brain},
  author={Q. Ni and Heng Xu and J. Partilla and B. Costa and K. Rice and H. Kayakiri and R. Rothman},
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), previous studies from our laboratory resolved two subtypes of the kappa 2 binding site, termed kappa 2a and kappa 2b. In more recent studies, we used 6 beta-[125Iodo]-3,14-dihydroxy-17-cyclopropylmethyl-4,5 alpha-epoxymorphinan ([125I]IOXY) to characterize multiple kappa 2 binding sites in rat brain. The results… Expand
κ Opioid Receptor Stimulation of [35S] GTPγS Binding in Guinea Pig Brain
Abstract Although only one gene for κ opioid receptors has been cloned to date, κ1 and κ2 receptors have been defined pharmacologically, with drugs such as bremazocine binding to both putative κExpand
Analysis of [3H]bremazocine binding in single and combinatorial opioid receptor knockout mice.
The data show that the putative kappa(2)-opioid receptors are in fact a mixed population of KOR, DOR and predominantly MOR gene products, confirming definitively that no additional gene is required to explain the total population of [3H]bremazocine binding sites. Expand
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
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. 12. Buprenorphine is a potent and selective μ/κ antagonist in the [35S]‐GTP‐γ‐S functional binding assay
Data indicated that, in this assay system, buprenorphine is a potent μ and γ receptor antagonist, and the clinical implications remain to be elucidated. Expand
κ2 Opioid Receptors in Limbic Areas of the Human Brain Are Upregulated by Cocaine in Fatal Overdose Victims
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
Oxycodone and morphine have distinctly different pharmacological profiles: Radioligand binding and behavioural studies in two rat models of neuropathic pain
Abstract Previously, we reported that oxycodone is a putative κ‐opioid agonist based on studies where intracerebroventricular (i.c.v.) pre‐treatment of rats with the κ‐selective opioid antagonist,Expand
Action of naloxone on gender-dependent analgesic and antianalgesic effects of nalbuphine in humans****
Coadministration of naloxone, which had no analgesic action administered alone, not only reversed the expected pain-enhancing effect of n albuphine in men, but produced a similar degree of long-lasting analgesia in both sexes, suggesting this drug combination might become an important new pharmacological therapy for pain relief. Expand
Effects of opioid analgesics on the action of general anaesthetics
The air-dried, milky exudation obtained by incising the unripe capsules of papaver somniferum, or its variety album, have been used for many hundreds of years to relieve pain. The chief narcoticExpand
Role of the opioid system in the behavioral deficit observed after uncontrollable shock
It is suggested that prior exposure to uncontrollable shock induces a kappa opioid mediated event that inhibits learning, and the role of the kappa receptor in the behavioral deficit is examined. Expand
Salvinorin A: the "magic mint" hallucinogen finds a molecular target in the kappa opioid receptor.
Based on the selectivity of salvinorin A for the KOR, this receptor represents a potential molecular target for the development of drugs to treat disorders characterized by alterations in perception, including schizophrenia, Alzheimer's disease and bipolar disorder. Expand


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
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 receptorsExpand
Interaction of endogenous opioid peptides and other drugs with four kappa opioid binding sites in guinea pig brain
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
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
Binding characteristics of kappa opioids in rat brain A comparison of in vitro binding paradigms
It is proposed that blocked [3H]ethylketocyclazocine is the more appropriate paradigm to study putative kappa binding, while blocked [ 3H]diprenorphine may label additional non-mu/non-delta sites. Expand
Evidence for multiple “kappa” binding sites by use of opioid peptides in the guinea-pig lumbo-sacral spinal cord
Pharmacological investigations indicate that DALI sites for which dynorphin (1 leads to 17) is the best ligand, can be related to kappa sites previously described in guinea-pig brain, whereas DALS sites, for which (Arg6, Phe7) Met-enkephalin possesses a good affinity, closely correspond to benzomorphan sites recently characterized in rat brain and spinal cord. Expand
Multiple agonist-affinity states of opioid receptors: regulation of binding by guanyl nucleotides in guinea pig cortical, NG108-15, and 7315c cell membranes.
Pertussis toxin treatment resulted in a monophasic agonist competition curve which was best fitted by a single-site model in both 7315c and NG108-15 cell membranes, and the effects of guanyl nucleotides were qualitatively similar at mu and delta receptors. Expand
Preparation of rat brain membranes highly enriched with opiate kappa binding sites using site-directed acylating agents: Optimization of assay conditions
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
Characterization and visualization of rat and guinea pig brain kappa opioid receptors: evidence for kappa 1 and kappa 2 opioid receptors.
Quantitative light microscopy in vitro autoradiography was used to visualize the neuroanatomical pattern of kappa receptors in rat and guinea pig brain, providing direct evidence for the presence of two kappa receptor subtypes. Expand
Interaction of Opiates with Opioid Binding Sites in the Bovine Adrenal Medulla: I. Interaction with δ and μ Sites
Kinetic and equilibrium binding studies revealed that in each case radiolabeled opiates interact with one class of binding sites, following simple second‐order bi molecular kinetics. Expand
Kappa 3: A novel subtype of the kappa opioid site in bovine adrenal medulla, highly selective for Met-enkephalin-Arg6-Phe7
It is proposed that this residual etorphine-identified site might represent a novel subtype of the kappa opioid site named kappa 3, and Met-enkephalin-Arg 6 Phe 7 might be its endogenous ligand. Expand