Opposite role of δ1- and δ2-opioid receptors activated by endogenous or exogenous opioid agonists on the endogenous cholecystokinin system: further evidence for δ-opioid receptor heterogeneity

Neuroscience ◽  
1996 ◽  
Vol 75 (3) ◽  
pp. 917-926 ◽  
Author(s):  
F. Noble ◽  
M.-C. Fournie-Zaluski ◽  
B.P. Roques
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Opioid Agonists ◽  
Δ Opioid Receptor

The K+-evoked release of [3H]acetylcholine from slices of rat globus pallidus: modulation by δ-opioid receptors

1991 ◽  
Vol 69 (3) ◽  
pp. 414-418 ◽  
Author(s):  
Bianca B. Ruzicka ◽  
Khem Jhamandas
Keyword(s):  
Globus Pallidus ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Cholinergic Neurons ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Release Of Acetylcholine ◽  
Δ Opioid Receptor ◽  
Tritium Release

Previous investigations have shown that the activation of δ-opioid receptors depresses the release of acetylcholine (ACh) in the rat caudate putamen. This finding raised the possibility that the release of ACh is similarly modulated in the globus pallidus, a region containing a distinct population of cholinergic neurons and enriched in enkephalinergic nerve terminals. In the present study the pallidal release of ACh was characterized and the effects of δ-opioid receptor activation on this release were examined. The results show that this release is stimulated by high K+ in a concentration- and Ca2+-dependent manner. D-Pen2,L-Pen5-enkephalin (0.1 – 10 μM), a selective δ-opioid receptor agonist, produced a dose-related inhibition of the 25 mM K+-evoked tritium release. The maximal inhibitory effect, representing a 34% decrease in the K+-induced tritium release, was observed at a concentration of 1 μM. This opioid effect was attenuated by the selective δ-opioid receptor antagonist, ICI 174864 (1 μM). These findings support the role of a δ-opioid receptor in the modulation of ACh release in the rat globus pallidus.Key words: globus pallidus, acetylcholine, enkephalin, release.

scholarly journals EFFECTS OF NEW PIPERIDINE DERIVATIVES WITH SUBSTITUTIONS IN THE 1ST AND 4TH POSITIONS IN NALOXONE SENSITIVE ANALGESY

2021 ◽  
Vol 19 (5) ◽  
pp. 501-505
Author(s):  
A. A. Vasilyuk ◽  
◽  
V. I. Kozlovsky ◽  
G. S. Akhmetova ◽  
V. K. Yu ◽  
...  
Keyword(s):  
Pain Relief ◽  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Analgesic Effect ◽  
Chemical Stimulation ◽  
Analgesic Action ◽  
Preliminary Administration ◽  
Chemical Irritation

Background. Despite the wide arsenal of painkillers, pain relief is an urgent interdisciplinary problem that requires a search for new solutions. Purpose of the study. To establish the role of opioid receptors in the mechanism of the analgesic action of the piperidine derivatives AGV-22 and AGV-23. Material and methods. The studies were carried out on 96 white mice of both sexes weighing 30-40 g. The analgesic effect of the compounds was tested on models of thermal and chemical irritation with preliminary administration of the opioid receptor antagonist naloxone. Results. The pain reactions of mice with models of thermal and chemical stimulation in the AGV-22 / AGV-23 + naloxone and AGV-22 / AGV-23 groups were comparable. Conclusions. The mechanism of the analgesic action of the piperidine derivatives AGV-22 and AGV-23 is not associated with the activation of opioid receptors.

scholarly journals Proteasome Involvement in Agonist-induced Down-regulation of μ and δ Opioid Receptors

2001 ◽  
Vol 276 (15) ◽  
pp. 12345-12355 ◽  
Author(s):  
Kirti Chaturvedi ◽  
Persis Bandari ◽  
Norihiro Chinen ◽  
Richard D. Howells
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Proteasome Inhibitors ◽  
Metabolic Labeling ◽  
Down Regulation ◽  
Hek 293 ◽  
293 Cells ◽  
Ubiquitin Proteasome ◽  
Μ Opioid Receptor ◽  
Δ Opioid Receptor

This study investigated the mechanism of agonist-induced opioid receptor down-regulation. Incubation of HEK 293 cells expressing FLAG-tagged δ and μ receptors with agonists caused a time-dependent decrease in opioid receptor levels assayed by immunoblotting. Pulse-chase experiments using [35S]methionine metabolic labeling indicated that the turnover rate of δ receptors was accelerated 5-fold following agonist stimulation. Inactivation of functional Giand Goproteins by pertussis toxin-attenuated down-regulation of the μ opioid receptor, while down-regulation of the δ opioid receptor was unaffected. Pretreatment of cells with inhibitors of lysosomal proteases, calpain, and caspases had little effect on μ and δ opioid receptor down-regulation. In marked contrast, pretreatment with proteasome inhibitors attenuated agonist-induced μ and δ receptor down-regulation. In addition, incubation of cells with proteasome inhibitors in the absence of agonists increased steady-state μ and δ opioid receptor levels. Immunoprecipitation of μ and δ opioid receptors followed by immunoblotting with ubiquitin antibodies suggested that preincubation with proteasome inhibitors promoted accumulation of polyubiquitinated receptors. These data provide evidence that the ubiquitin/proteasome pathway plays a role in agonist-induced down-regulation and basal turnover of opioid receptors.

Role of carboxyl terminus of μ- and δ-opioid receptor in agonist -induced down-regulation

1998 ◽  
Vol 54 (1) ◽  
pp. 24-34 ◽  
Author(s):  
Elham A Afify ◽  
Ping Y Law ◽  
Maureen Riedl ◽  
Robert Elde ◽  
Horace H Loh
Keyword(s):  
Opioid Receptor ◽  
Carboxyl Terminus ◽  
Down Regulation ◽  
Δ Opioid Receptor

Morphine initiates migrating myoelectric complexes by acting on peripheral opioid receptors

1985 ◽  
Vol 249 (5) ◽  
pp. G557-G562 ◽  
Author(s):  
G. L. Telford ◽  
M. Hoshmonai ◽  
A. J. Moses ◽  
J. H. Szurszewski
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Silver Chloride ◽  
Phase Iii ◽  
Opioid Receptor Antagonists ◽  
Peripheral Opioid Receptors ◽  
Silver Silver ◽  
Silver Silver Chloride ◽  
Higher Doses

The role of peripheral and central opioid receptors in morphine-induced migrating myoelectric complexes (MMECs) was studied in conscious dogs implanted with silver-silver chloride electrodes. In normal fasted dogs morphine (100-200 micrograms/kg iv) initiated phase III of the MMEC in the duodenum. Once initiated the MMEC propagated distally. This effect of morphine was blocked by the opioid receptor antagonists naloxone (2 mg/kg iv) and N,N-diallylnormorphinium bromide (4 mg/kg iv). Higher doses of morphine (300-600 micrograms/kg iv) initiated phase III activity in fed dogs as early as 20 min after feeding, while lower doses (150 micrograms/kg iv) initiated phase III activity routinely when administered 100 min after feeding. In dogs with bilateral vagotomies and bilateral thoracolumbar sympathetic chain ganglionectomies, morphine (150 micrograms/kg iv) initiated phase III activity in the duodenum, which then migrated distally. This study demonstrates that morphine initiates phase III of the MMEC by acting through peripheral opioid receptors.

scholarly journals TAN-67, a δ1-opioid receptor agonist, reduces infarct size via activation of Gi/oproteins and KATPchannels

1998 ◽  
Vol 274 (3) ◽  
pp. H909-H914 ◽  
Author(s):  
Jo El J. Schultz ◽  
Anna K. Hsu ◽  
Hiroshi Nagase ◽  
Garrett J. Gross
Keyword(s):  
Infarct Size ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Coronary Artery Occlusion ◽  
Receptor Activation ◽  
Artery Occlusion ◽  
Cardioprotective Effect ◽  
Area At Risk ◽  
Opioid Receptor Agonist ◽  
Δ Opioid Receptor

We have previously shown that delta (δ)-opioid receptors, most notably δ1, are involved in the cardioprotective effect of ischemic preconditioning (PC) in rats; however, the mechanism by which δ-opioid receptor-induced cardioprotection is mediated remains unknown. Therefore, we hypothesized that several of the known mediators of ischemic PC such as the ATP-sensitive potassium (KATP) channel and Gi/oproteins are involved in the cardioprotective effect produced by δ1-opioid receptor activation. To address these possibilities, anesthetized, open-chest Wistar rats were randomly assigned to five groups. Control animals were subjected to 30 min of coronary artery occlusion and 2 h of reperfusion. To demonstrate that stimulating δ1-opioid receptors produces cardioprotection, TAN-67, a new selective δ1-agonist, was infused for 15 min before the long occlusion and reperfusion periods. In addition, one group received 7-benzylidenenaltrexone (BNTX), a selective δ1-antagonist, before TAN-67. To study the involvement of KATPchannels or Gi/oproteins in δ1-opioid receptor-induced cardioprotection, glibenclamide (Glib), a KATPchannel antagonist, or pertussis toxin (PTX), an inhibitor of Gi/oproteins, was administered before TAN-67. Infarct size (IS) as a percentage of the area at risk (IS/AAR) was determined by tetrazolium stain. TAN-67 significantly reduced IS/AAR as compared with control (56 ± 2 to 27 ± 5%, n = 5, P < 0.05). The cardioprotective effect of TAN-67 was completely abolished by BNTX, Glib, and PTX (51 ± 3, 53 ± 5, and 61 ± 4%, n = 6 for each group, respectively). These results are the first to suggest that stimulating the δ1-opioid receptor elicits a cardioprotective effect that is mediated via Gi/oproteins and KATPchannels in the intact rat heart.

scholarly journals A Structure-Activity Relationship Comparison of Imidazodiazepines Binding at Kappa, Mu, and Delta Opioid Receptors and the GABAA Receptor

Molecules ◽  
2020 ◽  
Vol 25 (17) ◽  
pp. 3864
Author(s):  
Guanguan Li ◽  
Amanda N. Nieman ◽  
Md Yeunus Mian ◽  
Nicolas M. Zahn ◽  
Brandon N. Mikulsky ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Opioid Receptors ◽  
Hek293 Cells ◽  
Brain Extract ◽  
Gamma Aminobutyric Acid ◽  
Delta Opioid Receptors ◽  
Acid Type ◽  
Δ Opioid Receptor ◽  
Protein Recruitment ◽  
Competition Assays

Analgesic and anti-inflammatory properties mediated by the κ opioid receptor (KOR) have been reported for oxadiazole imidazodiazepines. Affinities determined by radioligand competition assays of more than seventy imidazodiazepines using cell homogenates from HEK293 cells that overexpress KOR, µ opioid receptor (MOR), and δ opioid receptor (DOR) are presented. Affinities to synaptic, benzodiazepine-sensitive receptors (BZR) were determined with rat brain extract. The highest affinity for KOR was recorded for GL-I-30 (Ki of 27 nM) and G-protein recruitment was observed with an EC50 of 32 nM. Affinities for MOR and DOR were weak for all compounds. Ester and amide imidazodiazepines were among the most active KOR ligands but also competed with 3H-flunitrazepam for brain extract binding, which is mediated predominately by gamma aminobutyric acid type A receptors (GABAAR) of the α1-3β2-3γ1-2 subtypes. Imidazodiazepines with carboxylic acid and primary amide groups did not bind KOR but interacted strongly with GABAARs. Pyridine substitution reduced KOR affinity. Oxadiazole imidazodiazepines exhibited good KOR binding and interacted weakly with BZR, whereas oxazole imidazodiazepines were more selective towards BZR. Compounds that lack the imidazole moiety, the pendent phenyl, or pyridine substitutions exhibited insignificant KOR affinities. It can be concluded that a subset of imidazodiazepines represents novel KOR ligands with high selectivity among opioid receptors.

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