Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P01189 (beta-endorphin)
 21,003 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bremazocine, a benzomorphan, has been reported to have kappa, mu and epsilon opioid receptor binding activities. The present studies were then designed to determine what types of opioid receptors and neurotransmitters were involved in inhibiting the tail-flick response induced by bremazocine in male ICR mice. U50, 488H, a prototypic kappa agonist, was used for comparison. Bremazocine, at doses from 0.1 to 1 microgram given i.c.v., dose-dependently inhibited the tail-flick response. The paw-licking hot plate response, even at high doses of bremazocine, was not completely inhibited. The inhibition of the tail-flick response induced by bremazocine (1 microgram) given i.c.v. was blocked by i.c.v. coadministration of beta-endorphin-(1-27) (3 and 6 micrograms), an epsilon opioid receptor antagonist and norbinaltorphimine (4 micrograms), a kappa opioid receptor antagonist. On the other hand, the inhibition induced by i.c.v. U50,488H (40 micrograms) was blocked by i.c.v. norbinaltorphimine, but not beta-endorphin-(1-27). D-Phe-Cys-Tyr-D-Try-Orn-Thr-Pen-Thr-NH2 (CTOP; 0.5 microgram) and beta-funaltrexamine (beta-FNA; 2.5 micrograms), selective mu opioid receptor antagonists, and ICI 174,864 (10 micrograms), a delta-opioid receptor antagonist, which blocked the effects induced by DAMGO (16 ng) and DPDPE (20 micrograms), respectively, did not block inhibition of the tail-flick response induced by bremazocine (1 microgram) given i.c.v. The inhibition of the tail-flick response induced by i.t. administration of bremazocine (1 microgram) was blocked by i.t. coadministration of norbinaltorphimine but not CTOP, ICI 174,864, or beta-endorphin-(1-27).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Involvement of epsilon and kappa opioid receptors in inhibition of the tail-flick response induced by bremazocine in the mouse. 165 27

Delta-opiate receptors have been solubilized with the non-ionic bile salt detergent digitonin from NG108-15 cell membranes and reconstituted into lipid vesicles. Specific opiate binding was restored to soluble receptor preparations after supplementation with a brain lipid extract, and dilution below the effective detergent concentration. Saturable and specific opiate binding was measured for both membrane and vesicle preparations; dissociation constants (Kd) obtained from saturation isotherms of [3H]bremazocine binding were 1.3 and 4.2 nM, respectively. Relative affinity (IC50) values of ligand binding measured for subtype-selective agonists confirmed that a delta-opiate binding site interaction was recovered in vesicle preparations. Changes in agonist binding affinity noted for these experiments were explained by dissociation of the GTP-binding protein Gi from the receptor in detergent. The recovery of solubilized opiate receptors was nearly quantitative, and strictly dependent upon the total brain lipid preparation used in the reconstitution. Ligand binding was incompletely recovered after substituting pure, vesicle-forming phospholipid preparations. [3H]Bremazocine binding was also reconstituted after lectin affinity chromatography of solubilized receptor preparations, using conditions which likely effect the removal of endogenous lipid cofactors. A photoaffinity cross-linking methodology was employed to verify recovery of the delta-opiate receptor after its solubilization from membranes and reconstitution. Two membrane-associated proteins (50 and 70 kDa) were covalently tagged with an azido analog of beta-endorphin(Leu5) in cell membranes and subsequently identified by immunoblotting with antisera directed against this opioid. Labeling of the 50-kDa polypeptide was prevented by coincubating assay samples with a relative excess of (D-Pen2,5)enkephalin. This opioid binding polypeptide was also present in solubilized/reconstituted receptor preparations.
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PMID:Reconstitution of solubilized delta-opiate receptor binding sites in lipid vesicles. 216 3

Adult female rats were implanted with permanent cannulae in the third ventricle of the brain and ovariectomized. 3 weeks later, blood samples were withdrawn every 5 min from intraatrial cannulae placed the previous day. After a control sampling period of 30 min, the rats received an intraventricular bolus injection of saline (2 microliter) or beta-endorphin (beta E; 10 micrograms); sampling was continued for an additional 2 h. Saline injection caused no effect on luteinizing hormone (LH) and prolactin (PRL) secretion. beta E stimulated PRL secretion within 5-10 min, the values peaked in the next 10 min. Thereafter, as PRL levels fell, a suppression of LH secretion became apparent. Inhibition of LH release started 20-35 min after beta E injection and lasted for 35-65 min. The antecendent PRL secretion was apparently not responsible for the observed delayed LH response, since blockade of PRL response with bromocriptine failed to affect the beta E-induced LH suppression. Further, continuous intraventricular infusion of beta E (5 or 10 micrograms/h) for 3 h markedly suppressed the amplitude and frequency of LH episodes in long-term ovariectomized rats. Bolus intraventricular injection of other endogenous opioid peptides and opiate receptor agonists produced different PRL and LH responses. Dynorphin (10 micrograms) similarly suppressed LH release but was only moderately effective in stimulating PRL. Leucine enkephalin (50 micrograms) stimulated LH and inhibited PRL release, while methionine-enkephalin (50 micrograms) selectively stimulated PRL release. The methionine-enkephalin analogs, FK-33824 (50 ng) and DALAMID (50 micrograms), evoked sequential PRL and LH responses similar to those seen after beta E injection. Interestingly, morphiceptin (a specific mu receptor agonist; 10 micrograms) markedly suppressed LH release, but only sparingly stimulated PRL release. Delta receptor peptide (a specific delta receptor agonist; 10 micrograms) selectively suppressed LH release. Bremazocine (a specific kappa receptor agonist; 0.5 mg/kg) administered intravenously suppressed LH release selectively. These studies show that of the four endogenous opioid peptides tested beta E was most effective in evoking sequential PRL and LH responses, and these effects may be mediated by either epsilon receptors or multiple opiate receptor subtypes; stimulation of kappa receptors by bynorphin or bremazocine suppressed LH release, and further studies would be needed to understand the mode of action of the two enkephalins and the delta opiate receptors in eliciting disparate PRL and LH responses.
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PMID:Effects of endogenous opioid peptides and opiates on luteinizing hormone and prolactin secretion in ovariectomized rats. 404 42

The role of the endogenous opioid peptide dynorphin (1-17) in regulating NMDA receptor-mediated synaptic currents was examined in guinea pig hippocampus. Schaffer collateral/commissural fiber-evoked NMDA synaptic currents were recorded using whole-cell patch-clamp techniques in CA3 pyramidal cells. Dynorphin was found to have dual effects on NMDA synaptic currents, increasing currents at low concentrations and decreasing currents at high concentrations. Only the inhibitory action of dynorphin was sensitive to naloxone, indicating that this effect was mediated by an opioid receptor. The inhibitory effect was mimicked by bremazocine, but not by U69,593, U50,488, [D-Ala2, N-Me-Phe4, Gly-ol]-enkephalin, or [D-Pen2,5]-enkephalin. Bremazocine's effect was blocked by naloxone, but not by nor-binaltorphimine, cyprodime, or naltrindole. These findings suggest that bremazocine's effect was mediated by the kappa 2 subtype of opioid receptor. In addition, 1 microM naloxone and antisera to dynorphin (1-17) were found to increase NMDA-mediated synaptic currents. Nor-binaltorphimine, cyprodime, naltrindole, and antisera to met-enkephalin did not increase the NMDA synaptic current. These findings suggest that endogenous dynorphin was acting at kappa 2 receptors to inhibit NMDA receptor-mediated synaptic currents. Overall, these findings indicate that dynorphin is an endogenous agonist for kappa 2 receptors in the CA3 region of the guinea pig hippocampus and that these receptors regulate NMDA receptor function.
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PMID:Kappa 2 opioid receptors inhibit NMDA receptor-mediated synaptic currents in guinea pig CA3 pyramidal cells. 791 46

Previous reports show the tail-flick inhibition induced by bremazocine given i.c.v. is mediated by supraspinal stimulation of both epsilon and kappa opioid receptors and the spinal activation of descending serotonergic and opioid systems. The present studies questioned what endogenous opioid peptides in the spinal cord were involved in i.c.v. bremazocine-induced antinociception in male ICR mice. beta-Endorphin, trans(+-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl]- benzene-acetamide methane sulfonate (U50,488H) and morphine were used as reference compounds for epsilon, kappa and mu opioid receptor activity, respectively. Intrathecal pretreatment with antibody to Met-enkephalin dose-dependently attenuated the antinociception induced by i.c.v. bremazocine or beta-endorphin but not morphine or U50,488H; whereas intrathecal (i.t.) pretreatment with antibody to dynorphin A (1-13) dose-dependently blocked the antinociception induced by i.c.v. bremazocine or U50,488H but not beta-endorphin or morphine. Intrathecal Leu-enkephalin and beta-endorphin antibodies did not block i.c.v. bremazocine, beta-endorphin or morphine antinociception. Intrathecal Met-enkephalin or dynorphin A (1-17) increased the tail-flick latency at 1 to 2 min. Met-enkephalin given i.t. blocked the antinociception induced by i.c.v. DPDPE, bremazocine and beta-endorphin but not morphine or U50,488H whereas i.t. dynorphin A (1-17) pretreatment blocked the inhibition induced by i.c.v. U50,488H and bremazocine but not DPDPE, beta-endorphin or morphine. Bremazocine given i.c.v. did not exhibit antianalgesic activity in our studies. The dynorphin released by i.c.v. bremazocine for antinociception appears to be different from the dynorphin released by morphine for antianalgesia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Spinal involvement of both dynorphin A and Met-enkephalin in the antinociception induced by intracerebroventricularly administered bremazocine but not morphine in the mouse. 810 94