Molecular Biology of Opioid Receptors: Recent Advances

Singh, Vijay K.; Bajpai, K.; Biswas, Sunetra; Haq, W.; Khan, Mahnoor; Mathur, K. B.

doi:10.1159/000097349

Cited by 39 publications

(24 citation statements)

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“…Several investigators have shown the effect of opioids on mitogen-and antigen-stimulated T cell proliferation in vitro through opioid receptors [1,26,27]. Both T and B lymphocytes have been shown to possess opioid receptors in a functional state [27].…”

Section: Discussionmentioning

confidence: 99%

“…One of the central problems in neuroimmunology is research on the influence of neurohormonal substances, particularly neuropeptides, on functions of the immune system [1]. In the recent past much attention has been paid to endogenous opioids that are known to possess not only neurotropic but also immunotropic properties.…”

Section: Introductionmentioning

confidence: 99%

“…Although there is no unanimity, ligands of Ì-and Î-opioid receptors primarily downregulate the immune system [7,8], while ‰ and Â ligands stimulate the immune system [1,[9][10][11]. The identification of endogenous peptide ligands for these opioid receptors has provided leads for designing receptorselective, biologically stable peptide molecules.…”

Section: Introductionmentioning

confidence: 99%

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Immunomodulation by Opioid Peptidomimetic Compound

Narayan¹,

Singh²,

Agarwal

et al. 2001

Neuroimmunomodulation

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Objective: As a follow-up to our earlier studies on immunomodulation with opioid peptides, we synthesized and evaluated immunomodulatory activity of four peptidomimetic compounds, i.e. Tyr-NH-C(Me)₂-CH₂-O-Phe-NH₂(1), Tyr-NH-C₆H₅-(o)-CH₂-CH₂-O-Phe-NH₂ (2), Tyr-NH-CH₂-CH₂-O-Phe-NH₂ (3) and Tyr-NH-CH(D-Et)-CH₂-O-Phe-NH₂ (4). Methods: These compounds were synthesized in solution phase and evaluated for their immunomodulatory properties in vitro by mixed lymphocyte reaction (MLR), proliferation of opioid receptor-expressing cells, production of tumor necrosis factor-α (TNF-α) and nitric oxide. Results: This study shows the immunosuppressive potential of synthetic peptidomimetic compound 3. This compound inhibited two-way MLR and suppressed the proliferation of the µ-opioid receptor expressing human embryonic kidney cells HEK 293 in vitro. Inhibition of MLR by compound 3 was reversed by naloxone (opioid receptor antagonist) and β-funaltrexamine hydrochloride (µ-opioid receptor antagonist). The immunosuppressive effect of compound 3 was further demonstrated by inhibition of TNF-α and nitric oxide production in lipopolysaccharide-stimulated human PBMCs and mouse macrophage cells RAW 264.7, respectively. Conclusion: These observations suggest that compound 3 inhibits MLR through µ-opioid receptor present on cells.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Immunomodulation by Opioid Peptidomimetic Compound

Narayan¹,

Singh²,

Agarwal

et al. 2001

Neuroimmunomodulation

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“…Opioid receptors are constitutively, or upon induction, expressed on the immune cells, and with respect to macrophages Ì, ‰ and Î receptor types (opioid receptor protein or transcript) were detected [23][24][25]. Opioid receptors cloned from the immune cells appeared to be identical to those from the neuronal cells [26]. Earlier pharmacological studies recognized various subtypes of three opioid receptor types, i.e.…”

Section: Introductionmentioning

confidence: 98%

Methionine-Enkephalin Stimulates Hydrogen Peroxide and Nitric Oxide Production in Rat Peritoneal Macrophages: Interaction of μ, δ and κ Opioid Receptors

Vujić

Stanojević

Dimitrijević

2004

Neuroimmunomodulation

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Objective: Methionine-enkephalin (MET) modulates various functions of macrophages related to both immune and inflammatory reactions in a naloxone reversible manner, suggesting that opioid receptors are involved in the regulation of macrophage activity. Since an endogenous opioid ligand might interact with more than one type of opioid receptor, the receptor interaction determines its effect on a particular function. Methods: In the present study we have investigated the involvement of different opioid receptor types/subtypes in MET-induced modulation of H₂O₂ and NO production in macrophages. Thioglycollate-elicited or resident rat peritoneal macrophages were treated in vitro with MET and/or specific antagonists of δ_1,2, δ₁, δ₂, µ and ĸ opioid receptors. Results: MET increased H₂O₂production inphorbol myristate acetate-stimulated rat peritoneal macrophages mainly through δ₁ opioid receptor. MET also enhanced NOproduction in rat peritoneal macrophages stimulated with lipopolysaccharide through δ₁ and µ opioid receptors. The blockade of µ and ĸ receptor facilitated a potentiating effect of MET on H₂O₂ release, and blockade of ĸ receptor further raised the MET-induced increase of NO production in macrophages. Conclusion: It is concluded that both negative and positive functional interaction between δ, µ and ĸ opioid receptors regulate the influence of MET on H₂O₂ and NO production in rat peritoneal macrophages.

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“…Ligands approach and engage GPCRs from the extracellular space, and receptor activation results in coupling to heterotrimeric G proteins on the intracellular face of membrane. The amino termini of nearly all G protein-coupled receptors contain consensus amino acid sequences for asparagine-linked glycosylation; two sites for N-linked glycosylation are present in ␦ and receptors, while five are found in the receptor (3).…”

mentioning

confidence: 99%

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

Chaturvedi

Bandari

Chinen

et al. 2001

Journal of Biological Chemistry

135

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This study investigated the mechanism of agonist-induced opioid receptor down-regulation. Incubation of HEK 293 cells expressing FLAG-tagged ␦ and receptors with agonists caused a time-dependent decrease in opioid receptor levels assayed by immunoblotting. Pulsechase experiments using [35 S]methionine metabolic labeling indicated that the turnover rate of ␦ receptors was accelerated 5-fold following agonist stimulation. Inactivation of functional G i and G o proteins by pertussis toxin-attenuated down-regulation of the opioid receptor, while down-regulation of the ␦ opioid receptor was unaffected. Pretreatment of cells with inhibitors of lysosomal proteases, calpain, and caspases had little effect on and ␦ opioid receptor down-regulation. In marked contrast, pretreatment with proteasome inhibitors attenuated agonist-induced and ␦ receptor down-regulation. In addition, incubation of cells with proteasome inhibitors in the absence of agonists increased steadystate and ␦ opioid receptor levels. Immunoprecipitation of and ␦ 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.The pharmacological effects of opioid drugs and the physiological effects of endogenous opioid peptides are initiated through the binding and activation of opioid receptors (1), which are members of the G protein-coupled receptor (GPCR) 1 family (2). GPCRs comprise a diverse superfamily of integral membrane proteins that mediate signal transduction across the plasma membrane. All GPCRs are postulated to have amino termini located on the extracellular side of the plasma membrane that are linked to seven-transmembrane helices connected by relatively short intracellular and extracellular loops, and contain carboxyl termini that face the interior of the cell. Ligands approach and engage GPCRs from the extracellular space, and receptor activation results in coupling to heterotrimeric G proteins on the intracellular face of membrane. The amino termini of nearly all G protein-coupled receptors contain consensus amino acid sequences for asparagine-linked glycosylation; two sites for N-linked glycosylation are present in ␦ and receptors, while five are found in the receptor (3).Three types of opioid receptor, ␦, , and , have been cloned and characterized extensively (4 -7). Opioid receptors have unique ligand specificities, anatomical distributions, and physiological functions (8 -15). Opioid receptors exhibit ϳ60% identity in their amino acid sequences, however, marked differences in sequence conservation are evident within receptor subdomains. The amino acid sequences of putative transmembrane spanning segments and the three intracellular loops are highly conserved among opioid receptor types, whereas sequences in the extracellular amino termini, second and third extracellular...

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Molecular Biology of Opioid Receptors: Recent Advances

Cited by 39 publications

References 0 publications

Immunomodulation by Opioid Peptidomimetic Compound

Immunomodulation by Opioid Peptidomimetic Compound

Methionine-Enkephalin Stimulates Hydrogen Peroxide and Nitric Oxide Production in Rat Peritoneal Macrophages: Interaction of μ, δ and κ Opioid Receptors

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

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