Pharmacological characterization of AR-M1000390 at human delta opioid receptors

Marie, Nicolas; Landemore, Gérard; Debout, Claire; Jauzac, Philippe; Allouche, Stéphane

doi:10.1016/s0024-3205(03)00489-2

Cited by 26 publications

(33 citation statements)

References 23 publications

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“…Similar observations were obtained for Kir3-channel currents recorded from d-Opioid Receptor Pharmacology oocytes in which the receptor was cotransfected with GRK2 and barr2 (Kovoor et al, 1997;Lowe et al, 2002). On the other hand, if receptors were expressed at very high levels, if concentrations of the desensitizing agonist were submaximal, or if partial agonists were used, desensitization occurred at a much slower rate (Bot et al, 1997;Kouhen et al, 2000;Law et al, 2000;Marie et al, 2003a;Qiu et al, 2007), with half-lives more than 10-fold slower than those of phosphorylation (Navratilova et al, 2007). The fact that DOPr phosphorylation contributes to its rapid desensitization is also supported by reports showing that truncation of the receptor or Ala substitution of all C-terminal Ser/Thr residues reduced the rate and maximal desensitization of Kir3 (Kovoor et al, 1997) and AC responses (Qiu et al, 2007).…”

Section: D-opioidsupporting

confidence: 72%

“…Two types of observations allow us to categorically conclude that internalization is not required for DOPr desensitization to take place: 1) sustained exposure (30 minutes to 3 hours) to ligands such as ARM100390 (Marie et al, 2003a;Pradhan et al, 2010) or TIPP (Hong et al, 2009) induces desensitization in systems in which they fail to induce internalization, and 2) replacement of Ser363 by Ala interferes with desensitization without affecting sequestration (Navratilova et al, 2007; but also see Law et al, 2000). On the other hand, as discussed in section VII.D on DOPr trafficking, the way in which internalization may influence the course of desensitization must be considered in relation to postendocytic routing and receptor targeting to recycling Archer-Lahlou et al, 2009;Audet et al, 2012;Gupta et al, 2014) and degradation (Tsao and von Zastrow, 2000;Whistler et al, 2002).…”

Section: D-opioidmentioning

confidence: 99%

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Molecular Pharmacology ofδ-Opioid Receptors

et al. 2016

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Section: D-opioidsupporting

confidence: 72%

Section: D-opioidmentioning

confidence: 99%

Molecular Pharmacology ofδ-Opioid Receptors

et al. 2016

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“…After a classical pharmacological characterization, which allowed us to determine the concentration of agonist producing similar inhibition of cAMP accumulation, we showed that the nonpeptidic agonist SNC-80 was able to induce a strong desensitization after a short pretreatment (30 min). This decrease in the ability of hDOR to inhibit adenylyl cyclase was comparable with the desensitization promoted by the two peptidic agonists DPDPE and deltorphin I (Allouche et al, 1999a) and by a nonpeptidic agonist AR-M1000390 (Marie et al, 2003b). In contrast, a slower desensitization was observed after exposure with enkephalins, because it was necessary to prolong time pretreatment until 120 min to obtain the same desensitization rate as with 30-min exposure to SNC-80.…”

Section: Discussionmentioning

confidence: 60%

Different Regulation of Human δ-Opioid Receptors by SNC-80 [(+)-4-[(αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide] and Endogenous Enkephalins

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Marie²,

Jauzac³

et al. 2004

J Pharmacol Exp Ther

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Among the different mechanisms underlying opioid tolerance, receptor desensitization would represent a major cellular adaptation process in which the role of receptor internalization is still a matter of debate. In the present study, we examined desensitization of the human ␦-opioid receptor (hDOR) produced by endogenous opioid peptides Leu-enkephalin (Tyr-Gly-Gly-PheLeu) and Met-enkephalin (Tyr-Gly-Gly-Phe-Met), and the contribution of internalization in this process. Results obtained with natural peptides were compared with those produced by a synthetic opioid agonist, SNC-80. After a 30-min treatment, we observed a different regulation of hDOR between agonists. SNC-80 produced a stronger and faster desensitization and was associated with a loss of opioid binding sites by 50%. SNC-80 also caused a marked hDOR down-regulation by 30% as observed by Western blot. Immunocytochemistry revealed that SNC-80 induced a complete redistribution of hDOR from cell surface into intracellular compartments, whereas a partial internalization was visualized upon enkephalin exposure. In constrast, a stronger hDOR recycling and resensitization were measured after enkephalin treatment compared with SNC-80. These data strongly suggested a differential sorting of the internalized receptors caused by enkephalins and SNC-80 that was further confirmed by chloroquine as a lysosomal degradation blocker and monensin as a recycling endosome inhibitor. Finally, by preventing hDOR internalization with 0.5 M sucrose, we demonstrated that hDOR internalization contributes partially to desensitization. In conclusion, hDOR desensitization depends both on its internalization and its sorting either to the recycling pathway or to lysosomes.The three opioid receptors, namely, ␦-, -, and -opioid receptors, are regulated not only by endogenous opioid peptides but also by numerous pharmacologically active drugs, particularly those used in the clinical management of pain (Reisine and Pasternak, 1996). These receptors belong to the superfamily of seven-transmembrane domain G protein-coupled receptors (GPCRs) and are subjected to the regulatory mechanisms described for the ␤2-adrenergic receptor, the prototypic GPCR. Similarly to many GPCRs, a sustained or repeated activation of opioid receptors by agonist results in a reduction of responsiveness known as desensitization that is postulated to underlie opioid tolerance in vivo (Loh et al., 1988). Recently, by using ␤-arrestin 2 knockout mice, Bohn et al. (2000) clearly established a direct link between opioid receptor desensitization and tolerance. Chronic treatment of these transgenic animals promoted neither tolerance to morphine-induced analgesia nor -opioid receptor desensitization evaluated using [35 S]guanosine 5Ј-O-(3-thio)triphosphate binding. Desensitization could result from uncoupling between opioid receptors and G proteins, whereas contribution of a decrease of opioid receptor number is less clear in this process. For example, a prolonged treatment (24 h) of the R1.1 cell line by (trans)...

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“…ARM390 (Wei et al, 2000) is a highly selective delta opioid receptor agonist, with similar receptor binding and G protein activation properties to SNC80 (Wei et al, 2000; Marie et al, 2003a; Payza, 2004; Pradhan et al, 2009). It has a greater selectivity for the delta opioid receptor than SNC80, and affinity for mu and kappa ~4000 and ~6000 fold greater.…”

Section: Introductionmentioning

confidence: 99%

The delta opioid receptor tool box

2016

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In recent years, the delta opioid receptor has attracted Increasing Interest as a target for the treatment of chronic pain and emotional disorders. Due to their therapeutic potential, numerous tools have been developed to study the delta opioid receptor from both a molecular and a functional perspective. This review summarizes the most commonly available tools, with an emphasis on their use and limitations. Here, we describe (1) the cell-based assays used to study the delta opioid receptor. (2) The features of several delta opioid receptor ligands, including peptide and non-peptide drugs. (3) The existing approaches to detect delta opioid receptors in fixed tissue, and debates that surround these techniques. (4) Behavioral assays used to study the in vivo effects of delta opioid receptor agonists; including locomotor stimulation and convulsions that are induced by some ligands, but not others. (5) The characterization of genetically modified mice used specifically to study the delta opioid receptor. Overall, this review aims to provide a guideline for the use of these tools with the final goal of increasing our understanding of delta opioid receptor physiology.

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Pharmacological characterization of AR-M1000390 at human delta opioid receptors

Cited by 26 publications

References 23 publications

Molecular Pharmacology ofδ-Opioid Receptors

Molecular Pharmacology ofδ-Opioid Receptors

Different Regulation of Human δ-Opioid Receptors by SNC-80 [(+)-4-[(αR)-α-((2S,5R)-4-Allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide] and Endogenous Enkephalins

The delta opioid receptor tool box

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