Skip to main content
SpringerLink
Log in

Opioid Receptors and Neuronal Signal Transduction

  • Chapter
  • First Online:
Opioids

Abstract

This chapter provides information on the classification, structure, and properties of the main opioid receptor subtypes, their canonical and non-canonical signaling pathways, and the variety of mechanisms influencing opioid signal transduction in neurons. Opioid receptors are members of the seven transmembrane G protein-coupled receptors. These receptors signal via inhibitory G proteins. The α subunit of G protein inhibits the adenylyl cyclase enzyme and reduces cyclic adenosine monophosphate and protein kinase A activity, altering gene expression. The βγ subunit increases K+ conductance and reduces Ca2+ entrance, causing hyperpolarization. Furthermore, a subset of endosomal signals arises after receptor phosphorylation and β-arrestin activation. Biased agonists and allosteric modulators regulate opioid receptor effects. Alternative splicing, polymorphisms, dimerization, and epigenetic factors also determine the heterogeneity, expression, and function of opioid receptors.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Pert CB, Pasternak G, Snyder SH. Opiate agonists and antagonists discriminated by receptor binding in brain. Science (80-). 1973;182:1359–61. https://doi.org/10.1126/science.182.4119.1359.

    Article  CAS  Google Scholar 

  2. Conibear AE, Kelly E. A biased view of μ-opioid receptors? Mol Pharmacol. 2019;96:542–9. https://doi.org/10.1124/mol.119.115956.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Darcq E, Kieffer BL. Opioid receptors: drivers to addiction? Nat Rev Neurosci. Springer US. 2018;19:499–514. https://doi.org/10.1038/s41583-018-0028-x.

    Article  CAS  Google Scholar 

  4. Cruz SL, Granados-Soto V. Opioids and opiates: pharmacology, abuse, and addiction. In: Pfaff DW, Volkow ND, editors. Neurosci 21st century. New York: Springer; 2016. p. 3625–57. https://doi.org/10.1007/978-1-4939-3474-4_156.

    Chapter  Google Scholar 

  5. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, Spedding M, et al. The concise guide to PHARMACOLOGY 2013/14: G protein-coupled receptors. Br J Pharmacol. John Wiley & Sons, Ltd. 2013;170:1459–581. https://doi.org/10.1111/bph.12445.

    Article  CAS  Google Scholar 

  6. Lemos Duarte M, Devi LA. Post-translational modifications of opioid receptors. Trends Neurosci. Elsevier. 2020;43:417–32. https://doi.org/10.1016/j.tins.2020.03.011.

    Article  CAS  Google Scholar 

  7. Wang S. Historical review: opiate addiction and opioid receptors. Cell Transplant. 2019;28:233–8. https://doi.org/10.1177/0963689718811060.

    Article  PubMed  Google Scholar 

  8. Livingston KE, Traynor JR. Allostery at opioid receptors: modulation with small molecule ligands. Br J Pharmacol. 2018;175:2846–56. https://doi.org/10.1111/bph.13823.

    Article  CAS  PubMed  Google Scholar 

  9. Chaturvedi K, Christoffers KH, Singh K, Howells RD. Structure and regulation of opioid receptors. Biopolymers. 2000;55:334–46. https://doi.org/10.1002/1097-0282(2000)55:4<334::AID-BIP1006>3.0.CO;2-S.

    Article  CAS  PubMed  Google Scholar 

  10. Stein C. New concepts in opioid analgesia [Internet]. Expert Opin Investig Drugs. Taylor & Francis. 2018;27(10):765–75. https://doi.org/10.1080/13543784.2018.1516204.

    Article  CAS  Google Scholar 

  11. Shang Y, Yeatman HR, Provasi D, Alt A, Christopoulos A, Canals M, et al. Proposed mode of binding and action of positive allosteric modulators at opioid receptors. ACS Chem Biol. 2016;11:1220–9. https://doi.org/10.1021/acschembio.5b00712.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Manglik A. Molecular basis of opioid action: from structures to new leads. Biol Psychiatry. 2020;87:6–14. https://doi.org/10.1016/j.biopsych.2019.08.028.

    Article  CAS  PubMed  Google Scholar 

  13. Che T, Roth BL. Structural insights accelerate the discovery of opioid alternatives. Annu Rev Biochem. 2021;90:739–61. https://doi.org/10.1146/annurev-biochem-061620-044044.

    Article  CAS  PubMed  Google Scholar 

  14. Marino KA, Shang Y, Filizola M. Insights into the function of opioid receptors from molecular dynamics simulations of available crystal structures. Br J Pharmacol. 2018;175:2834–45. https://doi.org/10.1111/bph.13774.

    Article  CAS  PubMed  Google Scholar 

  15. Marmolejo-Valencia AF, Madariaga-Mazón A, Martinez-Mayorga K. Bias-inducing allosteric binding site in mu-opioid receptor signaling. SN Appl Sci. Springer International Publishing. 2021;3:566. https://doi.org/10.1007/s42452-021-04505-8.

    Article  CAS  Google Scholar 

  16. Piltonen M, Krokhotin A, Parisien M, Bérubé P, Djambazian H, Sladek R, et al. Alternative splicing of opioid receptor genes shows a conserved pattern for 6TM receptor variants. Cell Mol Neurobiol. 2021;41:1039–55. https://doi.org/10.1007/s10571-020-00971-7.

    Article  CAS  PubMed  Google Scholar 

  17. Alexander SPH, Christopoulos A, Davenport AP, Kelly E, Mathie A, Peters JA, et al. THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors. Br J Pharmacol. 2019;176(S1). https://doi.org/10.1111/bph.14748.

  18. Remesic M, Hruby VJ, Porreca F, Lee YS. Recent advances in the realm of allosteric modulators for opioid receptors for future therapeutics. ACS Chem Neurosci. 2017;8:1147–58. https://doi.org/10.1021/acschemneuro.7b00090.

    Article  CAS  PubMed  Google Scholar 

  19. Quirion B, Bergeron F, Blais V, Gendron L. The delta-opioid receptor; a target for the treatment of pain. Front Mol Neurosci. 2020;13:52. https://doi.org/10.3389/fnmol.2020.00052.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Berthiaume S, Abdallah K, Blais V, Gendron L. Alleviating pain with delta opioid receptor agonists: evidence from experimental models. J Neural Transm. Springer Vienna. 2020;127:661–72. https://doi.org/10.1007/s00702-020-02172-4.

    Article  Google Scholar 

  21. Margolis EB, Karkhanis AN. Dopaminergic cellular and circuit contributions to kappa opioid receptor mediated aversion. Neurochem Int. Elsevier. 2019;129:104504. https://doi.org/10.1016/j.neuint.2019.104504.

    Article  CAS  Google Scholar 

  22. Faouzi A, Varga BR, Majumdar S. Biased opioid ligands. Molecules. 2020;25:4257. https://doi.org/10.3390/molecules25184257.

    Article  CAS  PubMed Central  Google Scholar 

  23. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, et al. Crystal structure of rhodopsin: a G protein-coupled receptor. Science. 2000;289:739–45. https://doi.org/10.1126/science.289.5480.739.

    Article  CAS  PubMed  Google Scholar 

  24. Koehl A, Hu H, Maeda S, Zhang Y, Qu Q, Paggi JM, et al. Structure of the μ-opioid receptor-Gi protein complex. Nature. 2018;558:547–52. https://doi.org/10.1038/s41586-018-0219-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Machelska H, Celik MÖ. Advances in achieving opioid analgesia without side effects. Front Pharmacol. 2018;9:1388. https://doi.org/10.3389/fphar.2018.01388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Proft J, Weiss N. G protein regulation of neuronal calcium channels: back to the future. Mol Pharmacol. 2015;87:890–906. https://doi.org/10.1124/mol.114.096008.

    Article  CAS  PubMed  Google Scholar 

  27. Canals M. The complex roles of μ-opioid receptor phosphorylation: a key determinant in receptor signaling and regulation. Mol Pharmacol. 2015;88:814–5. https://doi.org/10.1124/mol.115.100180.

    Article  CAS  PubMed  Google Scholar 

  28. Williams JT, Ingram SL, Henderson G, Chavkin C, von Zastrow M, Schulz S, et al. Regulation of μ-opioid receptors: desensitization, phosphorylation, internalization, and tolerance. Dolphin AC, editor. Pharmacol Rev. 2013;65:223–54. https://doi.org/10.1124/pr.112.005942.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Allouche S, Noble F, Marie N. Opioid receptor desensitization: mechanisms and its link to tolerance. Front Pharmacol. 2014;5:280. https://doi.org/10.3389/fphar.2014.00280.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Lemel L, Lane JR, Canals M. GRKs as key modulators of opioid receptor function. Cell. 2020;9:2400. https://doi.org/10.3390/cells9112400.

    Article  CAS  Google Scholar 

  31. Raehal KM, Schmid CL, Groer CE, Bohn LM. Functional selectivity at the μ-opioid receptor: implications for understanding opioid analgesia and tolerance. Sibley DR, editor. Pharmacol Rev. 2011;63:1001–19. https://doi.org/10.1124/pr.111.004598.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Bie B, Pan ZZ. Trafficking of central opioid receptors and descending pain inhibition. Mol Pain. 2007;3:37. https://doi.org/10.1186/1744-8069-3-37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Shenoy SK, Lefkowitz RJ. β-Arrestin-mediated receptor trafficking and signal transduction. Trends Pharmacol Sci. Elsevier Ltd. 2011;32:521–33. https://doi.org/10.1016/j.tips.2011.05.002.

    Article  CAS  Google Scholar 

  34. Delom F, Fessart D. Role of phosphorylation in the control of clathrin-mediated internalization of GPCR. Int J Cell Biol. 2011;2011:1–14. https://doi.org/10.1155/2011/246954.

    Article  CAS  Google Scholar 

  35. Reiter E, Ahn S, Shukla AK, Lefkowitz RJ. Molecular mechanism of β-arrestin-biased agonism at seven-transmembrane receptors. Annu Rev Pharmacol Toxicol. 2012;52:179–97. https://doi.org/10.1146/annurev.pharmtox.010909.105800.

    Article  CAS  PubMed  Google Scholar 

  36. Magalhaes AC, Dunn H, Ferguson SSG. Regulation of GPCR activity, trafficking and localization by GPCR-interacting proteins. Br J Pharmacol. 2012;165:1717–36. https://doi.org/10.1111/j.1476-5381.2011.01552.x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Dellibovi-Ragheb T, Altan-Bonnet N. Cloud storage for endosomes. EMBO J. 2016;35:1724–5. https://doi.org/10.15252/embj.201695080.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Che T, Dwivedi-Agnihotri H, Shukla AK, Roth BL. Biased ligands at opioid receptors: current status and future directions. Sci Signal. 2021;14:1–11. https://doi.org/10.1126/scisignal.aav0320.

    Article  CAS  Google Scholar 

  39. Pineyro G, Nagi K. Signaling diversity of mu- and delta-opioid receptor ligands: re-evaluating the benefits of β-arrestin/G protein signaling bias. Cell Signal. Elsevier Inc. 2021;80:109906. https://doi.org/10.1016/j.cellsig.2020.109906.

    Article  CAS  Google Scholar 

  40. Beaulieu J-M, Caron MG. β-Arrestin goes nuclear. Cell. 2005;123:755–7. https://doi.org/10.1016/j.cell.2005.11.010.

    Article  CAS  PubMed  Google Scholar 

  41. Kelly E. Efficacy and ligand bias at the μ-opioid receptor. Br J Pharmacol. John Wiley & Sons, Ltd. 2013;169:1430–46. https://doi.org/10.1111/bph.12222.

    Article  CAS  Google Scholar 

  42. Kliewer A, Gillis A, Hill R, Schmiedel F, Bailey C, Kelly E, et al. Morphine-induced respiratory depression is independent of β-arrestin2 signalling. Br J Pharmacol. 2020;177:2923–31. https://doi.org/10.1111/bph.15004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Kliewer A, Schmiedel F, Sianati S, Bailey A, Bateman JT, Levitt ES, et al. Phosphorylation-deficient G-protein-biased μ-opioid receptors improve analgesia and diminish tolerance but worsen opioid side effects. Nat Commun. Springer US. 2019;10:367. https://doi.org/10.1038/s41467-018-08162-1.

    Article  CAS  Google Scholar 

  44. Imam MZ, Kuo A, Ghassabian S, Smith MT. Progress in understanding mechanisms of opioid-induced gastrointestinal adverse effects and respiratory depression. Neuropharmacology. Elsevier Ltd. 2018;131:238–55. https://doi.org/10.1016/j.neuropharm.2017.12.032.

    Article  CAS  Google Scholar 

  45. Kaye AD, Cornett EM, Patil SS, Gennuso SA, Colontonio MM, Latimer DR, et al. New opioid receptor modulators and agonists. Best Pract Res Clin Anaesthesiol. Elsevier Ltd. 2018;32:125–36. https://doi.org/10.1016/j.bpa.2018.06.009.

    Article  Google Scholar 

  46. Pryce KD, Kang HJ, Sakloth F, Liu Y, Khan S, Toth K, et al. A promising chemical series of positive allosteric modulators of the μ-opioid receptor that enhance the antinociceptive efficacy of opioids but not their adverse effects. Neuropharmacology. Elsevier Ltd. 2021;195:108673. https://doi.org/10.1016/j.neuropharm.2021.108673.

    Article  CAS  Google Scholar 

  47. Gretton SK, Droney J. Splice variation of the mu-opioid receptor and its effect on the action of opioids. Br J Pain. 2014;8:133–8. https://doi.org/10.1177/2049463714547115.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Puig S, Gutstein HB. A “tail” of opioid receptor variants. J Clin Invest. 2017;127:1221–4. https://doi.org/10.1172/JCI93582.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Abbadie C, Pasternak GW. Differential in vivo internalization of MOR-1 and MOR-1C by morphine. Neuroreport. 2001;12:3069–72. https://doi.org/10.1097/00001756-200110080-00017.

    Article  CAS  PubMed  Google Scholar 

  50. Tanowitz M, Hislop JN, Von Zastrow M. Alternative splicing determines the post-endocytic sorting fate of G-protein-coupled receptors. J Biol Chem. © 2008 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. 2008;283:35614–21. https://doi.org/10.1074/jbc.M806588200.

    Article  CAS  Google Scholar 

  51. Narayan A, Hunkele A, Xu J, Bassoni DL, Pasternak GW, Pan YX. Mu opioids induce biased signaling at the full-length seven transmembrane C-terminal splice variants of the mu opioid receptor gene, OPRM1. Cell Mol Neurobiol. Springer US. 2021;41:1059–74. https://doi.org/10.1007/s10571-020-00973-5.

    Article  CAS  Google Scholar 

  52. Pasternak GW, Childers SR, Pan Y-X. Emerging insights into mu opioid pharmacology. Handb Exp Pharmacol. 2020;258:89–125. https://doi.org/10.1007/164_2019_270.

    Article  CAS  PubMed  Google Scholar 

  53. Convertino M, Samoshkin A, Viet CT, Gauthier J, Li Fraine SP, Sharif-Naeini R, et al. Differential regulation of 6- and 7-transmembrane helix variants of μ-opioid receptor in response to morphine stimulation. PLoS One. 2015;10:e0142826. https://doi.org/10.1371/journal.pone.0142826.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Xu J, Xu M, Brown T, Rossi GC, Hurd YL, Inturrisi CE, et al. Stabilization of the μ-opioid receptor by truncated single transmembrane splice variants through a chaperone-like action. J Biol Chem. © 2013 ASBMB. Currently published by Elsevier Inc; originally published by American Society for Biochemistry and Molecular Biology. 2013;288:21211–27. https://doi.org/10.1074/jbc.M113.458687.

    Article  CAS  Google Scholar 

  55. Robert F, Pelletier J. Exploring the impact of single-nucleotide polymorphisms on translation. Front Genet. 2018;9:507. https://doi.org/10.3389/fgene.2018.00507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Lötsch J, Geisslinger G. Relevance of frequent μ-opioid receptor polymorphisms for opioid activity in healthy volunteers. Pharmacogenomics J. 2006;6:200–10. https://doi.org/10.1038/sj.tpj.6500362.

    Article  CAS  PubMed  Google Scholar 

  57. Spampinato SM. Overview of genetic analysis of human opioid receptors. Methods Mol Biol. 2021;2201:3–13. https://doi.org/10.1007/978-1-0716-0884-5_1.

    Article  CAS  PubMed  Google Scholar 

  58. Bond C, LaForge KS, Tian M, Melia D, Zhang S, Borg L, et al. Single-nucleotide polymorphism in the human mu opioid receptor gene alters β-endorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci. 1998;95:9608–13. https://doi.org/10.1073/pnas.95.16.9608.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Margas W, Zubkoff I, Schuler HG, Janicki PK, Ruiz-Velasco V. Modulation of Ca2+ channels by heterologously expressed wild-type and mutant human μ-opioid receptors (hMORs) containing the A118G single-nucleotide polymorphism. J Neurophysiol. 2007;97:1058–67. https://doi.org/10.1152/jn.01007.2006.

    Article  CAS  PubMed  Google Scholar 

  60. Kroslak T, Laforge KS, Gianotti RJ, Ho A, Nielsen DA, Kreek MJ. The single nucleotide polymorphism A118G alters functional properties of the human mu opioid receptor. J Neurochem. 2007;103:77–87. https://doi.org/10.1111/j.1471-4159.2007.04738.x.

    Article  CAS  PubMed  Google Scholar 

  61. Knapman A, Santiago M, Connor M. A6V polymorphism of the human μ-opioid receptor decreases signalling of morphine and endogenous opioids in vitro. Br J Pharmacol. 2015;172:2258–72. https://doi.org/10.1111/bph.13047.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Befort K, Filliol D, Décaillot FM, Gavériaux-Ruff C, Hoehe MR, Kieffer BL. A single nucleotide polymorphic mutation in the human μ-opioid receptor severely impairs receptor signaling. J Biol Chem. 2001;276:3130–7. https://doi.org/10.1074/jbc.M006352200.

    Article  CAS  PubMed  Google Scholar 

  63. Wang D, Quillan JM, Winans K, Lucas JL, Sadée W. Single nucleotide polymorphisms in the human μ opioid receptor gene alter basal G protein coupling and calmodulin binding. J Biol Chem. 2001;276:34624–30. https://doi.org/10.1074/jbc.M104083200.

    Article  CAS  PubMed  Google Scholar 

  64. Crist RC, Clarke T-K. OPRD1 genetic variation and human disease. In: Jutkiewicz EM, editor. Delta opioid receptor pharmacology and therapeutic applications. Cham: Springer International Publishing; 2018. p. 131–45. https://doi.org/10.1007/164_2016_112.

    Chapter  Google Scholar 

  65. Gerra G, Leonardi C, Cortese E, D’Amore A, Lucchini A, Strepparola G, et al. Human kappa opioid receptor gene (OPRK1) polymorphism is associated with opiate addiction. Am J Med Genet B Neuropsychiatr Genet. 2007;144B:771–5. https://doi.org/10.1002/ajmg.b.30510.

    Article  CAS  PubMed  Google Scholar 

  66. Fujita W, Gomes I, Devi LA. Revolution in GPCR signalling: opioid receptor heteromers as novel therapeutic targets: IUPHAR review 10. Br J Pharmacol. 2014;171:4155–76. https://doi.org/10.1111/bph.12798.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. He L, Fong J, von Zastrow M, Whistler JL. Regulation of opioid receptor trafficking and morphine tolerance by receptor oligomerization. Cell. 2002;108:271–82. https://doi.org/10.1016/S0092-8674(02)00613-X.

    Article  CAS  PubMed  Google Scholar 

  68. Rozenfeld R, Abul-Husn NS, Gomez I, Devi LA. An emerging role for the delta opioid receptor in the regulation of mu opioid receptor function. Sci World J. 2007;7:64–73. https://doi.org/10.1100/tsw.2007.219.

    Article  Google Scholar 

  69. Zhang L, Zhang J, Hang L, Liu T. Mu opioid receptor heterodimers emerge as novel therapeutic targets: recent progress and future perspective. Front Pharmacol. 2020;11:1–11. https://doi.org/10.3389/fphar.2020.01078.

    Article  CAS  Google Scholar 

  70. Massotte D. In vivo opioid receptor heteromerization: where do we stand? Br J Pharmacol. 2015;172:420–34. https://doi.org/10.1111/bph.12702.

    Article  CAS  PubMed  Google Scholar 

  71. Reed B, Butelman ER, Yuferov V, Randesi M, Kreek MJ. Genetics of opiate addiction. Curr Psychiatry Rep. 2014;16:504. https://doi.org/10.1007/s11920-014-0504-6.

    Article  PubMed  Google Scholar 

  72. Smith H. Variations in opioid responsiveness. Pain Physician. 2008;11(2):237–48. https://doi.org/10.36076/ppj.2008/11/237.

    Article  PubMed  Google Scholar 

  73. Mistry CJ, Bawor M, Desai D, Marsh DC, Samaan Z. Genetics of opioid dependence: a review of the genetic contribution to opioid dependence. Curr Psychiatr Rev. 2014;10:156–67. https://doi.org/10.2174/1573400510666140320000928.

    Article  CAS  Google Scholar 

  74. Grim TW, Acevedo-Canabal A, Bohn LM. Toward directing opioid receptor signaling to refine opioid therapeutics. Biol Psychiatry. 2020;87:15–21. https://doi.org/10.1016/j.biopsych.2019.10.020.

    Article  CAS  PubMed  Google Scholar 

  75. Muñoa I, Urizar I, Casis L, Irazusta J, Subirán N. The epigenetic regulation of the opioid system: new individualized prompt prevention and treatment strategies. J Cell Biochem. 2015;116:2419–26. https://doi.org/10.1002/jcb.25222.

    Article  CAS  PubMed  Google Scholar 

  76. Browne CJ, Godino A, Salery M, Nestler EJ. Epigenetic mechanisms of opioid addiction. Biol Psychiatry. Elsevier Inc. 2020;87:22–33. https://doi.org/10.1016/j.biopsych.2019.06.027.

    Article  CAS  Google Scholar 

  77. Burford NT, Traynor JR, Alt A. Positive allosteric modulators of the μ-opioid receptor: a novel approach for future pain medications. Br J Pharmacol. John Wiley & Sons, Ltd. 2015;172:277–86. https://doi.org/10.1111/bph.12599.

    Article  CAS  Google Scholar 

  78. Burford NT, Clark MJ, Wehrman TS, Gerritz SW, Banks M, O’Connell J, et al. Discovery of positive allosteric modulators and silent allosteric modulators of the μ-opioid receptor. Proc Natl Acad Sci U S A. National Academy of Sciences. 2013;110:10830–5. https://doi.org/10.1073/pnas.1300393110.

    Article  Google Scholar 

  79. Livingston KE, Stanczyk MA, Burford NT, Alt A, Canals M, Traynor JR. Pharmacologic evidence for a putative conserved allosteric site on opioid receptors. Mol Pharmacol. 2018;93:157–67. https://doi.org/10.1124/mol.117.109561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Author notes

  1. César J. Carranza-Aguilar

    Present address: Institute of Neurobiology, National Autonomous University of Mexico, Juriquilla, Querétaro, Mexico

Authors and Affiliations

  1. Department of Pharmacobiology, Center for Research and Advanced Studies (Cinvestav), IPN, Mexico City, Mexico

    César J. Carranza-Aguilar, Zyanya P. Espinosa-Riquer, Frida L. Martínez-Cuevas & Silvia L. Cruz

  2. Opioids Working Group, Global Studies Seminar, Faculty of Medicine, National Autonomous University of Mexico, Mexico City, Mexico

    Silvia L. Cruz

Authors
  1. César J. Carranza-Aguilar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zyanya P. Espinosa-Riquer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frida L. Martínez-Cuevas
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Silvia L. Cruz
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacobiology, Cinvestav, Mexico City, Mexico

    Silvia L. Cruz

Rights and permissions

Reprints and permissions

Copyright information

© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Carranza-Aguilar, C.J., Espinosa-Riquer, Z.P., Martínez-Cuevas, F.L., Cruz, S.L. (2022). Opioid Receptors and Neuronal Signal Transduction. In: Cruz, S.L. (eds) Opioids. Springer, Cham. https://doi.org/10.1007/978-3-031-09936-6_9

Download citation

Publish with us

Policies and ethics

Search

Navigation