u-50488 and binaltorphimine
u-50488 has been researched along with binaltorphimine* in 9 studies
Other Studies
9 other study(ies) available for u-50488 and binaltorphimine
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Kappa opioid receptor controls neural stem cell differentiation via a miR-7a/Pax6 dependent pathway.
Although the roles of opioid receptors in neurogenesis have been implicated in previous studies, the mechanism by which κ-opioid receptor (OPRK1) regulates adult neurogenesis remains elusive. We now demonstrate that two agonists of OPRK1, U50,488H and dynorphin A, inhibit adult neurogenesis by hindering neuronal differentiation of mouse hippocampal neural stem cells (NSCs), both in vitro and in vivo. This effect was blocked by nor-binaltorphimine (nor-BNI), a specific antagonist of OPRK1. By examining neurogenesis-related genes, we found that OPRK1 agonists were able to downregulate the expression of Pax6, Neurog2, and NeuroD1 in mouse hippocampal NSCs, in a way that Pax6 regulates the transcription of Neurog2 and Neurod1 by directly interacting with their promoters. Moreover, this effect of OPRK1 was accomplished by inducing expression of miR-7a, a miRNA that specifically targeted Pax6 by direct interaction with its 3'-UTR sequence, and thereby decreased the levels of Pax6, Neurog2, and NeuroD1, thus resulted in hindrance of neuronal differentiation of NSCs. Thus, by modulating Pax6/Neurog2/NeuroD1 activities via upregulation of miR-7a expression, OPRK1 agonists hinder the neuronal differentiation of NSCs and hence inhibit adult neurogenesis in mouse hippocampus. Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Basic Helix-Loop-Helix Transcription Factors; Cell Differentiation; Dynorphins; Gene Expression Regulation, Developmental; Hippocampus; Humans; Mice; MicroRNAs; Naltrexone; Nerve Tissue Proteins; Neural Stem Cells; Neurogenesis; PAX6 Transcription Factor; Receptors, Opioid, kappa; Signal Transduction | 2021 |
Activation of the kappa-opioid receptor in Caco-2 cells decreases interleukin-8 secretion.
The immunomodulatory effects of kappa-opioid agonists at the intestinal epithelial level are not well characterized. In the present study, we determined that Caco-2 cells express the kappa-opioid receptor and its activation by trans-(+/-)-3,4-dichloro-N-methyl-N[2-(1-pyrolidinyl)cyclohexyl]benzeneacetamide methanesulfonate (U-50488) leads to decreased interleukin-8 secretion in the presence of interleukin-1beta. These effects were detected over a wide range (10 nM-50 microM) of U-50488 concentrations and were reversible using the kappa-opioid receptor antagonist nor-binaltorphimine. Our data suggest that activation of kappa-opioid receptors on Caco-2 cells decreases interleukin-8 secretion and thus may alter the chemotactic stimulus at the epithelial level. Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Adjuvants, Immunologic; Caco-2 Cells; Dose-Response Relationship, Drug; Humans; Immunohistochemistry; Interleukin-1; Interleukin-8; Naltrexone; Receptors, Opioid, kappa; Reverse Transcriptase Polymerase Chain Reaction | 2003 |
Modulatory effect of endogenous and exogenous opioids on the excitatory reflex pathway of the rat ileum.
The ascending excitatory reflex is part of the peristaltic reflex, an important participant in intestinal propulsion. The aim of this study was to characterize the role of different opioid receptors in the ascending reflex through exogenous application of non-selective (Met-enkephalin) and selective opioid agonists (mu-PLO17, delta-DPDPE, kappa-U-50, 488) as well as selective opioid receptor antagonists (mu: CTOP-NH(2), delta: ICI-174,864, kappa: Nor-Binaltorphimine). Metenkephalin (IC(50): 0.06 microM) and morphine (IC(50): 1.8 microM) inhibited the ascending reflex response concentration-dependently. Both the mu-selective agonist PLO17 (IC(50): 0.83 microM, n =11) and the kappa-selective agonist U-50,488 (IC(50): 0.68 microM, n =8) concentration-dependently inhibited the magnitude of the ascending contractile reflex response, whereas the delta-agonist DPDPE (10(-10)-10(-6)M) had no significant effect. In contrast, the latency of the response (time interval between start of the stimulus and onset of the contraction) was significantly prolonged by PLO17 > morphine > Met-enkephalin > DPDPE, whereas U-50,488 showed no effect. When the effect of the receptor-specific antagonists was tested, only CTOP-NH(2)and Nor-BNI caused a significant increase of the contractile response, whereas ICI-174 864 was ineffective. On the other hand, CTOP-NH(2)> ICI-174 864 decreased the latency significantly but the kappa-receptor agonist Nor-BNI had no influence. Thus, mu- and kappa-receptors seem to be involved in regulating the contraction strength of the ascending reflex, whereas both mu- and delta-receptors seem to be involved in the timing of the reflex response. Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Endorphins; Enkephalin, D-Penicillamine (2,5)-; Enkephalin, Leucine; Enkephalin, Methionine; Ileum; In Vitro Techniques; Male; Morphine; Muscle, Smooth; Naltrexone; Narcotic Antagonists; Narcotics; Peristalsis; Rats; Rats, Wistar; Receptors, Opioid; Somatostatin | 2000 |
Kappa opioid effects on fetal behavior: central administration of U50,488.
The kappa opioid agonist U50,488 was administered to E21 rat fetuses via intracisternal (IC), intrahemispheric (IH), or intrathecal (IT) injection. The IC administration of U50,488 promoted a threefold increase in motor activity, which was predominated by movements of caudal regions of the body (rearlimbs, body trunk, and tail). The agonist effect was reversed by IC administration of the selective kappa opioid antagonist nor-binaltorphimine. The IH injection of U50,488 had little effect on fetal behavior, but IT injection resulted in pronounced increases in fetal activity, including rearlimb, trunk, and tail movements. The IT administration of nor-binaltorphimine blocked U50,488 effects, whereas IH injection of the antagonist had little influence on fetal behavior. These findings suggest that kappa opioid receptors located in the spinal cord may play a role in the regulation of fetal motor behavior. Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Brain; Dose-Response Relationship, Drug; Female; Fetal Movement; Gestational Age; Injections, Intraventricular; Male; Naltrexone; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa | 1994 |
The modulation of placental lactogen release by opioids: a role for extracellular calcium.
We previously reported that kappa opioids stimulated the release of human placental lactogen (hPL) from trophoblastic cells and that this effect was prevented by co-incubation with naloxone. We also reported that adenylate cyclase was not directly involved in this process. In order to understand the post-receptor events mediating hPL release by opioids in the human placenta, we studied the role of extracellular calcium. Human trophoblastic cells obtained by trypsin digestion were cultured for 48 h in Ham's F-10 medium supplemented with 10% fetal bovine serum (FBS), 200 U/ml penicillin, and 200 micrograms/ml streptomycin. 45Ca2+ influx was then measured by filtration on glass-fiber filters. We observed a time- and dose-dependent stimulation of 45Ca2+ influx by ethylketocyclazocine (EKC) with an EC50 of 0.5 nM and a maximal stimulation of 196% over control. This effect was completely blocked by naloxone, a non-specific opioid antagonist, and by nor-binaltorphimine, a specific kappa antagonist. We also demonstrated that U-50,488 (kappa agonist) had the same stimulatory effect as EKC (221 +/- 25% of control). D-Ala2,NMe-Phe4,Gly-ol5)-enkephalin (DAGO) (mu agonist) slightly stimulated Ca2+ influx (128 +/- 5% of control, p > 0.05) whereas D-Ser2,Leu,Thr6)-enkephalin (DSLET) (delta agonist) had no effect. Pre-incubation of trophoblastic cells with pertussis toxin (PTX) did not affect the EKC-induced 45Ca2+ influx, suggesting that this placental opiate effect is not coupled with PTX-sensitive G proteins.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Adenylate Cyclase Toxin; Analgesics; Calcium; Cells, Cultured; Dopamine; Dose-Response Relationship, Drug; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Enkephalin, Leucine; Enkephalins; Ethylketocyclazocine; Gene Expression Regulation; Humans; Ionomycin; Naloxone; Naltrexone; Narcotics; Pertussis Toxin; Placental Lactogen; Pyrrolidines; Time Factors; Trophoblasts; Virulence Factors, Bordetella | 1993 |
The kappa-opioid receptor agonist U50,488H induces acute physical dependence in guinea-pigs.
The present study was undertaken to determine whether acute physical dependence occurred in guinea-pigs in vivo and guinea-pig isolated ileum following a single dose of the kappa-opioid receptor agonist U50,488H. Administration of naloxone hydrochloride, 15 and 30 mg/kg s.c., to guinea-pigs treated 1 h before with U50,488H, 10 mg/kg s.c., induced increased locomotor activity accompanied by behavioural responses which differed from those previously found in this species with morphine withdrawal. Nor-binaltorphimine, 10 mg/kg s.c., given 1 h after administration of U50,488H, 10 mg/kg s.c., produced a small but significant increase in locomotor activity but no other withdrawal behaviours. The morphine withdrawal response was not significantly affected by U50,488H, 1 or 10 mg/kg s.c. On the guinea-pig isolated ileum, nor-binaltorphimine, 1 microM, produced a withdrawal contracture following 2 min contact of the ileum with U50,488H 1 microM. U50,488H, 1 microM, abolished the [Met5]enkephalin withdrawal response of the ileum. It is concluded that dependence occurs following activation of kappa-opioid receptors, which is largely non-morphine-like in the central nervous system, but which is morphine-like in the enteric nervous system. Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics, Opioid; Animals; Behavior, Animal; Female; Guinea Pigs; Ileum; In Vitro Techniques; Male; Morphine Dependence; Motor Activity; Muscle Contraction; Muscle, Smooth; Naloxone; Naltrexone; Pyrrolidines; Receptors, Opioid, kappa; Substance Withdrawal Syndrome; Substance-Related Disorders | 1993 |
Mu- and kappa-opiate receptor control of prolactin secretion in rats: ontogeny and interaction with serotonin.
The present study explores developmental changes in mu- and kappa-opiate receptor control of PRL secretion. The ontogeny of mu- and kappa-receptor function was determined by assessing the PRL response to the mu-agonist sufentanil (SUF) and the kappa-agonist U50488 in 5-, 10-, 15-, 20-, and 60-day-old rats. Both mu- and kappa-agonists stimulated PRL secretion at all ages. The selectivity of the mu- and kappa-agonists was confirmed by selective blockade with their respective antagonists (beta-funaltrexamine and nor-binaltorphimine). Serotonin mediation of opiate-induced changes in PRL secretion was explored across ontogeny by testing cyproheptadine (CYPRO) blockade of agonist responses in 5-, 10-, 20-, and 60-day-old rats. CYPRO attenuated the PRL response to the mu-agonist SUF in 20- and 60-day-old rats, but not in the 5- or 10-day-old pups. CYPRO did not block the kappa-agonist U50488 at any age. Similarly, pretreatment with parachlorophenylalaine lowered the PRL response to SUF in 60-day-old rats, but not in 10-day-old rats. These results support previous reports of a serotonin-mediated mu control of PRL secretion that develops by day 20 and a kappa control of PRL secretion that is independent of serotonin at all ages. These findings also suggest that a previously reported serotonin-independent mu-receptor-mediated control of PRL secretion can be stimulated early in ontogeny. Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Aging; Animals; Cyproheptadine; Female; Kinetics; Male; Naltrexone; Prolactin; Pyrrolidines; Rats; Rats, Sprague-Dawley; Receptors, Opioid, kappa; Receptors, Opioid, mu; Serotonin; Sufentanil | 1992 |
Further evidence for the implication of a kappa-opioid receptor mechanism in the production of psychological stress-induced analgesia.
The analgesic effect induced by exposure to psychological stress, using a communication box (psychological stress-induced analgesia, PSY-SIA), was completely antagonized by 10 min pretreatment with 0.5, 1 and 2 mg/kg of nor-binaltorphimine and with 0.5 and 1 mg/kg of Mr2266, selective kappa-opioid receptor antagonists, in the tail pinch method. Neither footshock (FS)- nor forced swimming (SW)-SIA was affected by these antagonists. The selective delta-opioid receptor antagonist naltrindole, at doses up to 20 mg/kg, had no appreciable effect on PSY-SIA. Daily morphine treatment, 10 mg/kg, s.c., resulted in tolerance to the analgesic effect, and concurrent exposure to PSY-stress suppressed the development of morphine tolerance. The substitution of treatment with U-50,488H for PSY-stress still resulted in analgesia on the initial day; and likewise, the suppression by U-50,488H of the development of morphine tolerance was replicated by PSY-stress. Pretreatment with nor-binaltorphimine antagonized the suppressive effect of PSY-stress on the development of morphine tolerance without affecting the analgesic effect of morphine per se. These results provide further evidence that PSY-SIA involves the mediation by kappa-opioid receptor mechanisms. Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesia; Analgesics; Animals; Benzomorphans; Drug Tolerance; Electroshock; Indoles; Male; Mice; Mice, Inbred Strains; Morphinans; Morphine; Naltrexone; Narcotic Antagonists; Pyrrolidines; Receptors, Opioid; Receptors, Opioid, kappa; Stress, Psychological; Swimming | 1990 |
Binaltorphimine and nor-binaltorphimine, potent and selective kappa-opioid receptor antagonists.
The opioid antagonist activities of two bivalent ligands, BNI and nor-BNI, have been evaluated in smooth muscle preparations and in mice. Both ligands are highly potent and selective as kappa opioid receptor antagonists, with relatively feeble blocking activity at mu and delta opioid receptors. BNI and nor-BNI represent the first highly selective kappa opioid receptor antagonists and should be of great utility as molecular probes for identifying the interaction of agonist ligands with kappa opioid receptors in vitro and in vivo. Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Chemical Phenomena; Chemistry; Cyclazocine; Dynorphins; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Ethylketocyclazocine; Guinea Pigs; Male; Mice; Morphine; Naloxone; Naltrexone; Pyrrolidines; Rabbits; Receptors, Opioid; Receptors, Opioid, kappa | 1987 |