Synthesis and Evaluation of Isothiocyanate-Containing Derivatives of the δ-Opioid Receptor Antagonist Tyr-Tic-Phe-Phe (TIPP) as Potential Affinity Labels for δ-Opioid Receptors

2000 ◽  
Vol 43 (26) ◽  
pp. 5044-5049 ◽  
Author(s):  
Dean Y. Maeda ◽  
Fred Berman ◽  
Thomas F. Murray ◽  
Jane V. Aldrich
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Affinity Labels ◽  
Opioid Receptor Antagonist ◽  
Δ Opioid Receptor ◽  
Derivatives Of

Synaptic Actions of Neuropeptide FF in the Rat Parabrachial Nucleus: Interactions With Opioid Receptors

2000 ◽  
Vol 84 (2) ◽  
pp. 744-751 ◽  
Author(s):  
Xihua Chen ◽  
Jeffrey A. Zidichouski ◽  
Kim H. Harris ◽  
Jack H. Jhamandas
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Distribution Curve ◽  
Parabrachial Nucleus ◽  
Synaptic Currents ◽  
Opioid Receptor Antagonist ◽  
Neuropeptide Ff ◽  
Δ Opioid Receptor ◽  
Synaptic Effects

The pontine parabrachial nucleus (PBN) receives both opioid and Neuropeptide FF (NPFF) projections from the lower brain stem and/or the spinal cord. Because of this anatomical convergence and previous evidence that NPFF displays both pro- and anti-opioid activities, this study examined the synaptic effects of NPFF in the PBN and the mechanisms underlying these effects using an in vitro brain slice preparation and the nystatin-perforated patch-clamp recording technique. Under voltage-clamp conditions, NPFF reversibly reduced the evoked excitatory postsynaptic currents (EPSCs) in a dose-dependent fashion. This effect was not accompanied by apparent changes in the holding current, the current-voltage relationship or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–induced inward currents in the PBN cells. When a paired-pulse protocol was used, NPFF increased the ratio of these synaptic currents. Analysis of miniature EPSCs showed that NPFF caused a rightward shift in the frequency-distribution curve, whereas the amplitude-distribution curve remained unchanged. Collectively, these experiments indicate that NPFF reduces the evoked EPSCs through a presynaptic mechanism of action. The synaptic effects induced by NPFF (5 μM) could not be blocked by the specific μ-opioid receptor antagonist,d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2(1 μM), but application of δ-opioid receptor antagonist Tyr-Tic-Phe-Phe (5 μM) almost completely prevented effects of NPFF. Moreover, the δ-opioid receptor agonist, Deltorphin (1 μM), mimicked the effects as NPFF and also occluded NPFF's actions on synaptic currents. These results indicate that NPFF modulates excitatory synaptic transmission in the PBN through an interaction with presynaptic δ-opioid receptors. These observations provide a cellular basis for NPFF enhancement of the antinociceptive effects consequent to central activation of δ-opioid receptors.

scholarly journals Activation of δ-Opioid Receptors Reduces Excitatory Input to Putative Gustatory Cells Within the Nucleus of the Solitary Tract

2009 ◽  
Vol 101 (1) ◽  
pp. 258-268 ◽  
Author(s):  
Mingyan Zhu ◽  
Young K. Cho ◽  
Cheng-Shu Li
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Polymerase Chain Reaction Analysis ◽  
Excitatory Input ◽  
Solitary Tract ◽  
Opioid Receptor Antagonist ◽  
Naltrexone Hydrochloride ◽  
Parabrachial Nuclei ◽  
Δ Opioid Receptor

The rostral nucleus of the solitary tract (NST) is the first central relay in the gustatory pathway and plays a key role in processing and modulation of gustatory information. Here, we investigated the effects of opioid receptor agonists and antagonists on synaptic responses of the gustatory parabrachial nuclei (PbN)-projecting neurons in the rostral NST to electrical stimulation of the solitary tract (ST) using whole cell recordings in the hamster brain stem slices. ST-evoked excitatory postsynaptic currents (EPSCs) were significantly reduced by met-enkephalin (MetE) in a concentration-dependent fashion and this effect was eliminated by naltrexone hydrochloride, a nonselective opioid receptor antagonist. Bath application of naltrindole hydrochloride, a selective δ-opioid receptor antagonist, eliminated MetE-induced reduction of EPSCs, whereas CTOP, a selective μ-opioid receptor antagonist had no effect, indicating that δ-opioid receptors are involved in the reduction of ST-evoked EPSCs induced by MetE. SNC80, a selective δ-opioid receptor agonist, mimicked the effect of MetE. The SNC80-induced reduction of ST-evoked EPSCs was eliminated by 7-benzylidenenaltrexone, a selective δ1-opioid receptor antagonist but not by naltriben mesylate, a selective δ2-opioid receptor antagonist, indicating that δ1-opioid receptors mediate the reduction of ST-evoked EPSCs induced by SNC80. Single-cell reverse transcriptase–polymerase chain reaction analysis revealed the presence of δ1-opioid receptor mRNA in cells that responded to SNC80 with a reduction in ST-evoked EPSCs. Moreover, Western blot analysis demonstrated the presence of 40-kDa δ-opioid receptor proteins in the rostral NST tissue. These results suggest that postsynaptic δ1-opioid receptors are involved in opioid-induced reduction of ST-evoked EPSCs of PbN-projecting rostral NST cells.

scholarly journals The opioid placebo analgesia is mediated exclusively through µ-opioid receptor in rat

2013 ◽  
Vol 16 (4) ◽  
pp. 849-856 ◽  
Author(s):  
Rui-Rui Zhang ◽  
Wen-Cai Zhang ◽  
Jin-Yan Wang ◽  
Jian-You Guo
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Placebo Response ◽  
Anterior Cingulate ◽  
Sprague Dawley ◽  
Placebo Analgesia ◽  
Opioid Receptor Antagonist ◽  
Sprague Dawley Rats ◽  
Δ Opioid Receptor

Abstract Placebo analgesia is one of the most robust and best-studied placebo effects. Recent researches suggest that placebo analgesia activated the µ-opioid receptor signalling in the human brain. However, whether other opioid receptors are involved in the placebo analgesia remains unclear. We have previously evoked placebo responses in mice (Guo et al.2010, 2011) and these mice may serve as a model for investigating placebo analgesia. In the present study, we tried to explore the site of action and types of opioid receptors involved in placebo response. Male Sprague–Dawley rats were trained with 10 mg/kg morphine for 4 d to establish the placebo analgesia model. This placebo analgesia can be blocked by injection of 5 mg/kg dose naloxone or by microinjection with naloxone (1, 3 or 10 µg/rat) into rostral anterior cingulate cortex (rACC). Then, animals were tested after intra-rACC microinjection of d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP, a selective µ-opioid receptor antagonist) or naltrindole (NTI, a highly selective δ-opioid receptor antagonist) or nor-binaltorphimine (nor-BNI, a highly selective κ-opioid receptor antagonist). Our results showed that CTOP, but not NTI or nor-BNI, could reduce the pain threshold in placebo analgesia rats. It may be concluded that rACC is the key brain region involved in placebo analgesia and the opioid placebo analgesia is mediated exclusively through µ-opioid receptor in rat.

kappa-Opioid antagonist improves cellular bioenergetics and recovery after traumatic brain injury

1991 ◽  
Vol 261 (6) ◽  
pp. R1527-R1532 ◽  
Author(s):  
R. Vink ◽  
P. S. Portoghese ◽  
A. I. Faden
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Neurological Outcome ◽  
Kappa Opioid Receptors ◽  
Kappa Opioid ◽  
Opioid Receptor Antagonist ◽  
Cellular Bioenergetics

Treatment with opioid receptor antagonists improves outcome after experimental brain trauma, although the mechanisms underlying the protective actions of these compounds remain speculative. We have proposed that endogenous opioids contribute to the pathophysiology of traumatic brain injury through actions at kappa-opioid receptors, possibly by affecting cellular bioenergetic state. In the present study, the effects of the kappa-selective opioid-receptor antagonist nor-binaltorphimine (nor-BNI) were examined after fluid percussion brain injury in rats. Metabolic changes were evaluated by 31P magnetic resonance spectroscopy; the same animals were subsequently followed over 2 wk to evaluate neurological recovery. Nor-BNI, administered intravenously as a 10 or 20 mg/kg bolus at 30 min after injury, significantly improved neurological outcome at 2 wk posttrauma compared with controls. Animals treated with nor-BNI showed significantly greater recovery of intracellular free magnesium concentrations and cytosolic phosphorylation potentials during the first 4 h after injury compared with saline-treated controls. The improvement in cytosolic phosphorylation potential was significantly correlated to neurological outcome. These data support the hypothesis that kappa-opioid receptors mediate pathophysiological changes after traumatic brain injury and that the beneficial effects of opioid-receptor antagonist may result from improvement of posttraumatic cellular bioenergetics.

Behavioral effects of benzylideneoxymorphone (BOM), a low efficacy µ opioid receptor agonist and a δ opioid receptor antagonist

2020 ◽  
Vol 237 (12) ◽  
pp. 3591-3602
Author(s):  
Sanjana Mada ◽  
Lisa R. Gerak ◽  
Amélie Soyer ◽  
David R. Maguire ◽  
Zehua Hu ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Receptor Agonist ◽  
Behavioral Effects ◽  
Opioid Receptor Antagonist ◽  
Opioid Receptor Agonist ◽  
Δ Opioid Receptor

Protection of cardiac myocytes via δ1-opioid receptors, protein kinase C, and mitochondrial KATP channels

2001 ◽  
Vol 280 (1) ◽  
pp. H377-H383 ◽  
Author(s):  
Joon Huh ◽  
Garrett J. Gross ◽  
Hiroshi Nagase ◽  
Bruce T. Liang
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Receptor Antagonist ◽  
Cardiac Myocytes ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Inhibitory Effect ◽  
Cardioprotective Effect ◽  
Opioid Receptor Antagonist ◽  
Kinase C

The objective of the present study was to investigate the role of δ1-opioid receptors in mediating cardioprotection in isolated chick cardiac myocytes and to investigate whether protein kinase C and mitochondrial ATP-sensitive K+(KATP) channels act downstream of the δ1-opioid receptor in mediating this beneficial effect. A 5-min preexposure to the selective δ1-opioid receptor agonist (−)-TAN-67 (1 μM) resulted in less myocyte injury during the subsequent prolonged ischemia compared with untreated myocytes. 7-Benzylidenenaltrexone, a selective δ1-opioid receptor antagonist, completely blocked the cardioprotective effect of (−)-TAN-67. Naltriben methanesulfonate, a selective δ2-opioid receptor antagonist, had only a slight inhibitory effect on (−)-TAN-67-mediated cardioprotection. Nor-binaltorphimine dihydrochloride, a κ-opioid receptor antagonist, did not affect (−)-TAN-67-mediated cardioprotection. The protein kinase C inhibitor chelerythrine and the KATP channel inhibitors glibenclamide, a nonselective KATP antagonist, and 5-hydroxydecanoic acid, a mitochondrial selective KATPantagonist, reversed the cardioprotective effect of (−)-TAN-67. These results suggest that the δ1-opioid receptor is present on cardiac myocytes and mediates a potent cardioprotective effect via protein kinase C and the mitochondrial KATP channel.

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