Opioid Receptor
Opioid receptors are expressed by central and peripheral neurons and by neuroendocrine (pituitary, adrenal), immune, and ectodermal cells. Early binding studies and bioassays defined three main types of opioid receptors in the central nervous system, the mu, delta, and kappa receptors. Additional receptor types were proposed (e.g., sigma, epsilon, orphanin) but are no longer considered “classical” opioid receptors. The identification and sequence analysis of complementary DNA (cDNA) and the selective deletion of opioid receptor genes in mice confirmed the existence of only three genes. Opioid receptors belong to the class A gamma subgroup of seven transmembrane G protein–coupled receptors (GPCRs) and show 50–70% homology between their genes.
Additional pharmacologic subtypes may result from alternative splicing, posttranslational modifications, and/or receptor oligomerization. Opioid receptor activation leads to opening of G protein–coupled inwardly rectifying K+ (GIRK) channels, thereby preventing neuronal excitation and/or propagation of action potentials. Opioids also inhibit Na+ channels, Ih channels, transient receptor potential vanilloid-1 (TRPV1) channels, and acid-sensing ion channels (ASICs) in DRG neurons, as well as excitatory postsynaptic currents evoked by glutamate receptors in the spinal cord. Various kinases can phosphorylate intracellular regions of opioid receptors, and GPCR kinases promote binding of arrestin molecules. The formation of arrestin–opioid receptor complexes leads to opioid receptor desensitization by preventing G protein coupling and promotes receptor internalization via clathrin-dependent pathways. Recycling of dephosphorylated opioid receptors and their reintegration into the plasma membrane reinstates signal transduction, whereas targeting to lysosomes leads to receptor degradation. Opioid peptide-containing circulating leukocytes extravasate upon activation of adhesion molecules and chemotaxis by chemokines.
Subsequently, these leukocytes are stimulated by stress or releasing agents to secrete opioid peptides. For example, corticotropin-releasing factor (CRF), interleukin-1β (IL-1), and noradrenaline (NA, released from postganglionic sympathetic neurons) can elicit opioid release by activating their respective CRF receptors (CRFR), IL-1 receptors (IL-1R), and adrenergic receptors (AR) on leukocytes. Exogenous opioids (EOs) or endogenous opioid peptides (OPs, green triangles) bind to opioid receptors (ORs) that are synthesized in dorsal root ganglia and transported along intraaxonal microtubules to peripheral (and central) terminals of sensory neurons.
References
1.Stein C. Annu Rev Med. 2016;67:433–451.
Additional pharmacologic subtypes may result from alternative splicing, posttranslational modifications, and/or receptor oligomerization. Opioid receptor activation leads to opening of G protein–coupled inwardly rectifying K+ (GIRK) channels, thereby preventing neuronal excitation and/or propagation of action potentials. Opioids also inhibit Na+ channels, Ih channels, transient receptor potential vanilloid-1 (TRPV1) channels, and acid-sensing ion channels (ASICs) in DRG neurons, as well as excitatory postsynaptic currents evoked by glutamate receptors in the spinal cord. Various kinases can phosphorylate intracellular regions of opioid receptors, and GPCR kinases promote binding of arrestin molecules. The formation of arrestin–opioid receptor complexes leads to opioid receptor desensitization by preventing G protein coupling and promotes receptor internalization via clathrin-dependent pathways. Recycling of dephosphorylated opioid receptors and their reintegration into the plasma membrane reinstates signal transduction, whereas targeting to lysosomes leads to receptor degradation. Opioid peptide-containing circulating leukocytes extravasate upon activation of adhesion molecules and chemotaxis by chemokines.
Subsequently, these leukocytes are stimulated by stress or releasing agents to secrete opioid peptides. For example, corticotropin-releasing factor (CRF), interleukin-1β (IL-1), and noradrenaline (NA, released from postganglionic sympathetic neurons) can elicit opioid release by activating their respective CRF receptors (CRFR), IL-1 receptors (IL-1R), and adrenergic receptors (AR) on leukocytes. Exogenous opioids (EOs) or endogenous opioid peptides (OPs, green triangles) bind to opioid receptors (ORs) that are synthesized in dorsal root ganglia and transported along intraaxonal microtubules to peripheral (and central) terminals of sensory neurons.
References
1.Stein C. Annu Rev Med. 2016;67:433–451.
Endocrinology/Hormones
Opioid Receptor
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beta-Neoendorphin acetate(77739-21-0 free base)
产品货号 : M37922
cas no: 78658-39-6
beta-Neoendorphin acetate is an agonist of κ-opioid receptor -
Apitegromab
产品货号 : M36899
cas no: 2278276-46-1
Apitegromab (SRK-015) 是一种抗肌生长抑制素单克隆抗体。Apitegromab 可用于包括脊髓性肌萎缩症在内的神经肌肉疾病的研究。 -
Endomorphin 1 acetate
产品货号 : M36458
cas no: 1276123-71-7
Endomorphin 1 acetate,一种高度选择性的,高亲和力的 μ-opioid 受体激动剂 (Ki: 1.11 nM),对 kappa3结合位点具有高亲和力,Ki 值为 20 到 30 nM 之间。Endomorphin 1 acetate 具有镇痛特性。 -
Samidorphan HCl
产品货号 : M36054
cas no: 2328045-02-7
Samidorphan HCl is an orally active and highly potent modulator of the opioid system that binds to μ‐opioid, κ‐opioid, and delta-opioid receptors. Samidorphan HCl is a novel μ-opioid receptor antagonist, a partial agonist for k-opioid and delta-opioid receptors. Samidorphan HCl can be used to prevent and treat schizophrenia. -
6-GNTI dihydrochloride
产品货号 : M35173
cas no: 2410327-94-3
6'-GNTI dihydrochloride ,一种 κ-阿片受体 (KOR) 激动剂,在 β-arrestin2 募集过程中,显示出对 G 蛋白介导的信号激活的偏向。6'-GNTI dihydrochloride 只激活纹状体神经元的 Akt 通路。