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2017, 01, v.26 65-68
中枢μ阿片受体磷酸化与阿片耐受的相关性研究进展
基金项目(Foundation): 国家自然科学基金(编号81102643); 浙江省自然科学基金(编号LY14H270016、LQ15H270003); 中国博士后基金(编号2014M550334); 浙江省医药卫生科研基金(编号2014KYA162)
邮箱(Email):
DOI: 10.19577/j.cnki.issn10074406.2017.01.018
发布时间: 2017-01-25
出版时间: 2017-01-25
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摘要:

作用于中枢神经系统的μ阿片受体(MOR)激动剂是有效的止痛药,但长期或慢性使用可产生耐受。MOR的C末端位点的磷酸化介导受体失敏是引起阿片耐受关键性因素,而激动剂诱导MOR选择性的Ser375\Thr370\Thr376\Thr379位点磷酸化调控受体内吞,从而对抗耐受。除了GRKs、PKC,可能与PKC-JNK、GRK2、β-arrestin依赖途径及其他通路有关。

Abstract:

KeyWords:
参考文献

[1]CONNOR M,OSBOME PB,CHRISTIE MJ.Mu-opioid receptor desensitization:is morphine different[J].Br J Pharmacol,2004,143(6):685.

[2]LEFKOWITZ RJ.Historical review:a brief history and personal retrospective of seven-transmembrane receptors[J].Trends Pharmacol Sci,2004,25(8):413.

[3]SIM-SELLEY LJ,SELLEY DE,VOGT LJ,et al.Chronic heroin self-administration desensitizes mu opioid receptor-activated G-proteins in specific regions of rat brain[J].J Neurosci,2000,20(12):4555.

[4]HE L,WHISTLER JL.Chronic ethanol consumption in rats produces opioid antinociceptive tolerance through inhibition of mu opioid receptor endocytosis[J].PLo S ONE,2011,6(5):e19372.

[5]BAILEY CP,SMITH FL,KELLY E,et al.How important is protein kinase C in mu-opioid receptor desensitization and morphine tolerance[J].Trends Pharmacol Sci,2006,27(11):558.

[6]BAILEY CP,OLDFIELD S,LLORENTE J,et al.Involvement of PKC alpha and G-protein-coupled receptor kinase 2 in agonist-selective desensitization of mu-opioid receptors in mature brain neurons[J].Br J Pharmacol,2009,158(1):157.

[7]INGRAM SL,MACEY TA,FOSSUM EN,et al.Tolerance to repeated morphine administration is associated with increased potency of opioid agonists[J].Neuropsychopharmacology,2008,33(10):2494.

[8]吕庆琴,陈霆隽,洪炎国.μ阿片受体的内吞抑制吗啡耐受的形成[J].中国临床药理学与治疗学,2012,17(10):1185.

[9]QUELCH DR,KATSOURI L,NUTT DJ,et al.Imaging endogenous opioid peptide release with[11C]carfentanil and[3H]diprenorphine:influence of agonist-induced internalization[J].J Cereb Blood Flow Metab,2014,34(10):1604.

[10]DANG VC,CHRISTIE MJ.Mechanisms of rapid opioid receptor desensitization,resensitization and tolerance in brain neurons[J].Br J Pharmacol,2012,165(6):1704.

[11]ARTTAMANGKUL S,QUILLINAN N,LOW MJ,et al.Differential activation and trafficking of micro-opioid receptors in brain slices[J].Mol Pharmacol,2008,74(4):972.

[12]NOWOCZYN M,MARIE N,COULBAULT L,et al.Remifentanil produces cross-desensitization and tolerance with morphine on the mu-opioid receptor[J].Neuropharmacology,2013,73:368.

[13]MCPHERSON J,RIVERO G,BAPTIST M,et al.μ-opioid receptors:correlation of agonist efficacy for signalling with ability to activate internalization[J].Mol Pharmacol,2010,78(4):756.

[14]KELLY E.The subtleties ofμ-opioid receptor phosphorylation[J].Br J Pharmacol,2011,164(2):294.

[15]DOLL C,KONIETZKOJ,PLL F,et al.Agonist-selective patterns ofμ-opioid receptor phosphorylation revealed by phosphositespecific antibodies[J].Br J Pharmacol,2011,164(2):298.

[16]LAU EK,TRESTER-ZEDLITZ M,TRINIDAD JC,et al.Quantitative encoding of the effect of a partial agonist on individual opioidreceptors by multisite phosphorylation and threshold detection[J].Sci Signal,2011,4(185):ra52.

[17]CHEN YJ,OLDFIELD S,BUTCHER AJ,et al.Identification of phosphorylation sites in the COOH-terminal tail of theμ-opioid receptor[J].J Neurochem,2013,124(2):189.

[18]CHU J,ZHENG H,LOH HH,et al.Morphine-inducedμ-opioid receptor rapid desensitization is independent of receptor phosphorylation andβ-arrestins[J].Cell Signal,2008,20(9):1616.

[19]SCHULZ S,MAYER D,PFEIFFER M,et al.Morphine induces terminal micro-opioid receptor desensitization by sustained phosphorylation of serine-375[J].EMBO J,2004,23(16):3282.

[20]DOLL C,PLL F,PEUKER K,et al.Decipheringμ-opioid receptor phosphorylation and dephosphorylation in HEK293 cells[J].Br J Pharmacol,2012,167(6):1259.

[21]JUST S,ILLING S,TRESTER-ZEDLITZ M,et al.Differentiation of opioid drug effects by hierarchical multi-site phosphorylation[J].Mol Pharmacol,2013,83(3):633.

[22]MANN A,ILLING S,MIESS E,et al.Different mechanisms of homologous and heterologousμ-opioid receptor phosphorylation[J].Br J Pharmacol,2014,172(2):311.

[23]GRECKSCH G,JUST S,PIERSTORFF C,et al.Analgesic tolerance to high-efficacy agonists but not to morphine is diminished in phosphorylation-deficient S375Aμ-opioid receptor knock-in mice[J].J Neurosci,2011,31(39):13890.

[24]WILLIAMS JT,INGRAM SL,HENDERSON G,et al.Regulation ofμ-opioid receptors:desensitization,phosphorylationlation,internalization,and tolerance[J].Pharmacological Reviews,2013,65(1):223.

[25]FENG B,LI Z,WANG JB.Protein kinase C-mediated phosphorylation of theμ-opioid receptor and its effects on receptor signaling[J].Mol Pharmacol,2011,79(4):768.

[26]ILLING S,MANN A,SCHULZ S.Heterologous regulation of agonist-independentμ-opioid receptor phosphorylation by protein kinase C[J].Br J Pharmacol,2014,171(5):1330.

[27]WANG HL.A cluster of Ser/Thr residues at the C-terminus of muopioid receptor is required for G protein-coupled receptor kinase 2-mediated desensitization[J].Neuropharmacology,2000,39(3):353.

[28]GLCK L,LOKTEY A,MOULDOUS L,et al.Loss of morphine reward and dependence in mice lacking G protein-coupled receptor kinase 5[J].Biol Psychiatry,2014,76(10):767.

[29]项荣,胡艳,曹贝贝.β-Arrestins参与GPCRs信号通路的分子机制[J].中国生物化学与分子生物学报,2013,29(2):122.

[30]DANG VC,CHIENG B,AZRIEL Y,et al.Cellular morphine tolerance produced byβarrestin-2-dependent impairment ofμ-opioid receptor resensitization[J].J Neurosci,2011,31(19):7122.

[31]DANG VC,CHIENG BC,CHRISTIE MJ.Prolonged stimulation ofμ-opioid receptors producesβ-arrestin-2-mediated heterologous desensitization ofα(2)-adrenoceptor function in locus ceruleus neurons[J].Mol Pharmacol,2012,82(3):473.

[32]KUHAR JR,BEDINI A,MELIEF EJ,et al.Mu opioid receptor stimulation activates c-Jun N-terminal kinase 2 by distinct arrestindependent and independent mechanisms[J].Cell Signal,2015,27(9):1799.

[33]WAGLEY Y,HWANG CK,LIN HY,et al.Inhibition of c-Jun NH2-terminal kinase stimulates mu opioid receptor expression via p38 MAPK-mediated nuclear NF-κB activation in neuronal and nonneuronal cells[J].Biochim Biophys Acta,2013,1833(6):1476.

[34]ZANRINGHALAM J,TEKIEH E,MANAHEJI H,et al.Cellular events during arthritis-induced hyperalgesia are mediated by interleukin-6 and p38 MAPK and their effects on the expression of spinal mu-opioid receptors[J].Rheumatol Int,2013,33(9):2291.

基本信息:

DOI:10.19577/j.cnki.issn10074406.2017.01.018

中图分类号:R96

引用信息:

[1]付桃芳,杜俊英,王玲玲,等.中枢μ阿片受体磷酸化与阿片耐受的相关性研究进展[J].中国临床药学杂志,2017,26(01):65-68.DOI:10.19577/j.cnki.issn10074406.2017.01.018.

基金信息:

国家自然科学基金(编号81102643); 浙江省自然科学基金(编号LY14H270016、LQ15H270003); 中国博士后基金(编号2014M550334); 浙江省医药卫生科研基金(编号2014KYA162)

发布时间:

2017-01-25

出版时间:

2017-01-25

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