Skip to main content
SpringerLink
Log in

Functional analysis of cloned opioid receptors in transfected cell lines

  • Stimulatory Effects of Opioids
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Opioids modulate numerous central and peripheral processes including pain perception, neuroendocrine secretion and the immune response. The opioid signal is transduced from receptors through G proteins to various different effectors. Heterogeneity exists at all levels of the transduction process. There are numerous endogenous ligands with differing selectivities for at least three distinct opioid receptors (μ, δ, κ). G proteins activated by opioid receptors are generally of the pertussis toxin-sensitive Gi/Go class, but there are also opioid actions that are thought to involve Gq and cholera toxin-sensitive G proteins. To further complicate the issue, the actions of opioid receptors may be mediated by G-protein α subunits and/or βγ subunits. Subsequent to G protein activation several effectors are known to orchestrate the opioid signal. For example activation of opioid receptors increases phosphatidyl inositol turnover, activates K+ channels and reduces adenylyl cyclase and Ca2+ channel activities. Each of these effectors shows considerable heterogeneity. In this review we examine the opioid signal transduction mechanism. Several important questions arise: Why do opioid ligands with similar binding affinities have different potencies in functional assays? To which Ca2+ channel subtypes do opioid receptors couple? Do opioid receptors couple to Ca2+ channels through direct G protein interactions? Does the opioid-induced inhibition of vesicular release occur through modulation of multiple effectors? We are attempting to answer these questions by expressing cloned opioid receptors in GH3 cells. Using this well characterized system we can study the entire opioid signal transduction process from ligand-receptor interaction to G protein-effector coupling and subsequent inhibition of vesicular release.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Akil, H., Watson, S. J., Young, E., Lewis, M. E., Khachaturian, H., and Walker, J. M. 1984. Endogenous opioids: Biology and function. Ann. Rev. Neurosci. 7:223–255.

    Article  PubMed  CAS  Google Scholar 

  2. Schafer, M. K., and Martin, R. 1994. Oploid peptides in the pituitary: a hormone, a paracrine modulator and a peptide in search of function. Biol. Chem. Hoppe-Seyler. 375:737–740.

    PubMed  CAS  Google Scholar 

  3. Genazzani, A. R., and Petraglia, F. 1989. Opioid control of leutenizing hormone secretion in humans. J. Steroid Biochem. 33: 751–755.

    Article  PubMed  CAS  Google Scholar 

  4. Russell, J. A., Leng, G., and Bicknell, R. J. 1995. Opioid tolerance and dependence in the magnocellular oxytocin system: a physiological mechanism. 80:307–340.

  5. Maggi, R., Pimpinelli, F., Martini, L., and Piva, F. 1995. Inhibition of leuteinizing hormone-releasing hormone secretion by deltaopioid agonists in GT1-1 neuronal cells. Endocrinol. 136:5177–5181.

    Article  CAS  Google Scholar 

  6. Evans, C. J., Erdelyi, E., and Barchas, J. D. 1986. Candidate opioid peptides for interaction with the immune system. Pages 3–15,in Plotnikoff, N. P., Faith, R. E., Murgo, A. J., and Good, R. A. (eds.) Enkephalins and Endorphins-Stress and the Immune System, Plenum Press, New York.

    Google Scholar 

  7. Brown, S. M., Stimmel, B., Taub, R. N., Kochwa, S., and Rosenfield, R. E. 1974. Immunologic dysfunction in heroin addicts. Arch. Intern. Med. 134:1001–1014.

    Article  PubMed  CAS  Google Scholar 

  8. Milligan, C. E., Webster, L., Piros, E. T., Evans, C. J., Cunningham, T. J., and Levitt, P. 1995. Induction of opioid receptor-mediated macrophage chemotactic activity after neonatal brain injury. J. Immunol. 154:6571–6581.

    PubMed  CAS  Google Scholar 

  9. Basbaum, A. I., and Fields, H. L. 1984. Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Ann. Rev. Neurosci. 7:309–338.

    Article  PubMed  CAS  Google Scholar 

  10. Willis, W. D., Haber, L. H., and Martin, R. F. 1977. Inhibition of spinothalamic tract cells and interneurons by brain stem stimulation in the monkey. J. Neurophysiol. 40:968–981.

    PubMed  CAS  Google Scholar 

  11. Besson, J. M., and Chaouch, A. 1987. Peripheral and spinal mechanisms of nociception. Physiol. Rev. 67:67–196.

    PubMed  CAS  Google Scholar 

  12. MacDonald, R. L., and Nelson, P. G. 1978. Specific-opiate-induced depression of transmitter release from dorsal root ganglion cells in culture. Science Wash. DC 199:1449–1451.

    Article  CAS  Google Scholar 

  13. Mudge, A., Leeman, S. E., and Fischbach, G. D. 1979. Enkephalin inhibits release of substance P from sensory neurons in culture and decreases action potential duration. Proc. Natl. Acad. Sci. USA 76:526–530.

    Article  PubMed  CAS  Google Scholar 

  14. Yaksh, T. L. 1993. The spinal actions of opioids Pages 53–90,in Herz, A. (ed.), Opioids II, Handbook of Experimental Pharmacology, Springer-Verlag, Berlin.

    Google Scholar 

  15. Wollemann, M. 1990. Recent developments in the research of opioid receptor subtype molecular characterization. J. Neurochem. 54:1095–1101.

    Article  PubMed  CAS  Google Scholar 

  16. Evans, C. J., Keith, Jr., D. E., Morrison, H., Magendzo, K., and Edwards, R. H. 1992. Cloning of a delta opioid receptor by functional expression. Science 258:1952–1955.

    Article  PubMed  CAS  Google Scholar 

  17. Kieffer, B. L., Befort, K., Gaveriaux-Ruff, C., and Hirth, C. G. 1992. The delta-opioid receptor: isolation of a cDNA by expression cloning and pharmacological characterization. Proc. Natl. Acad. Sci. U. S. A. 89:12048–12052.

    Article  PubMed  CAS  Google Scholar 

  18. Chen, Y., Mestek, A., Liu, J., Hurley, J. A., and Yu, L. 1993. Molecular cloning and functional expression of a mu-opioid receptor from rat brain. Mol. Pharmacol. 44:8–12.

    PubMed  CAS  Google Scholar 

  19. Yasuda, K., Raynor, K., Kong, H., Breder, C. D., Takeda, J., Reisine, T., and Bell, G. I. 1993. Cloning and functional comparison of kappa and delta opioid receptors from mouse brain. Proc. Natl. Acad. Sci. U. S. A. 90:6736–6740.

    Article  PubMed  CAS  Google Scholar 

  20. Law, P. Y. 1995. G-proteins and opioid receptors' functions. Pages 109–130,in Tseng, L. F. (ed.) The Pharmacology of Opioid Peptides, Harwood Academic Publishers, Singapore.

    Google Scholar 

  21. Childers, S. R. 1991. Oploid receptor-coupled second messenger systems. Life Sci. 48:1991–2003.

    Article  PubMed  CAS  Google Scholar 

  22. North, R. A. 1991. Opioid receptor types and membrane ion channels. Trends Neurosci. 9:114–117.

    Article  Google Scholar 

  23. Huang, L. M. 1995. Cellular mechanisms of excitatory and inhibitory actions of opioids. Pages 131–149,in Tseng, L. F. (ed.), The Pharmacology of Opioid Peptides, Harwood Academic Publishers, Singapore.

    Google Scholar 

  24. Nestler, E. J. 1992. Molecular mechanisms of drug addiction. J. Neurosci. 12:2439–2450.

    PubMed  CAS  Google Scholar 

  25. Tai, K. K., Bian, C. F., and Wong, T. M. 1992. κ-Opioid receptor stimulation increases intracellular free calcium in isolated rat ventricular myocytes. Life Sci. 51:909–913.

    Article  PubMed  CAS  Google Scholar 

  26. Murthy, K. S., and Makhlouf, G. M. 1995. Adenosine A1 receptor-mediated activation of phospholipase C-β3 in intestinal muscle: dual requirement for α and βγ subunits of G13. Mol. Pharmacol. 47:1172–1179.

    PubMed  CAS  Google Scholar 

  27. Connor, M., and Henderson, G. 1996. δ and μ opioid receptor mobilization of intracellular calcium in SH-SY5Y cells. Br. J. Pharmacol. 117:334–341.

    Article  Google Scholar 

  28. Cruciani, R. A., Dvorkin, B., Morris, S. A., Crain, S. M., and Makman, M. H. 1993. Direct coupling of opioid receptors to both stimulatory and inhibitory guanine nucleotide binding proteins in F-11 neuroblastoma-sensory neuron hybrid cells. Proc. Natl. Acad. Sci. USA. 90:3019–3023.

    Article  PubMed  CAS  Google Scholar 

  29. Fan, S. F., Shen, K. F., and Crain, S. M. 1991. Opioids at low concentrations decrease openings of K+ channels in sensory ganglion cells. Brain Res. 558:166–170.

    Article  PubMed  CAS  Google Scholar 

  30. Piros, E. T., Prather, P. L., Loh, H. H., Law, P. Y., Evans, C. J., and Hales, T. G. 1995. Ca2+ channel and adenylyl cyclase modulation by cloned μ-opioid receptors in GH3 cells. Mol. Pharmacol. 47:1041–1049.

    PubMed  CAS  Google Scholar 

  31. Piros, E. T., Prather, P. L., Law, P. Y., Evans, C. J., and Hales, T. G. 1996. Vottage-dependent inhibition of Ca2+ channels in GH3 cells by cloned μ- and δ-opioid receptors. Mol. Pharmacol. In press.

  32. Delahunty, T. M., Cronin, M. J., and Linden, J. 1988. Regulation of GH3 cell function via adenosine A1 receptors: Inhibition of prolactin release, cyclic AMP production and inositol phosphate generation. Biochem J. 255:69–77.

    PubMed  CAS  Google Scholar 

  33. Scherubl, H., Hescheler, J., and Riecken, E. O. 1993. Molecular mechanisms of somatostatin's inhibition of hormone release: participation of voltage-gated calcium channels and G-proteins. Horm. Metab. Res. Suppl. 27:1–4.

    Google Scholar 

  34. Koch, B. D., Blalock, J. B., and Schonbrunn, A. 1988. Characterization of the cyclic AMP-independent actions of somatostatin in GH3 cells I. An increase in potassium conductance is responsible for both the hyperpolarization and the decrease in intracellular free calcium produced by somatostatin. J. Biol. Chem. 263: 216–225.

    PubMed  CAS  Google Scholar 

  35. Piros, E. T., Zaki, P., Edwards, R. H., Evans, C. J., and Hales, T. G. 1994. Functional expression of the mouse delta opioid receptor in a pituitary cell line. Neuroscience Abstracts 20:1731.

    Google Scholar 

  36. Akiyama, K., Gee, K. W., Mosberg, H. L., Hruby, V. J., and Yamamura, H. I. 1985. Characterization of [3H][2-D-penicillamine, 5-D-penicillamine]-enkephalin binding to delta opiate receptors in the rat brain and neuroblastoma-glioma hybrid cell line (NG 108-15). Proc. Natl. Acad. Sci. USA. 82:2543–2547.

    Article  PubMed  CAS  Google Scholar 

  37. Goldstein, A. 1987. Binding selectivity profiles for ligands of multiple receptor types: focus on opioid receptors. Trends Pharmacol. Sci. 8:456–459.

    Article  CAS  Google Scholar 

  38. Corbett, A. D., Paterson, S. J., and Kosterlitz, H. W. 1993. Selectivity of ligands for opioid receptors. Handb. Exp. Pharmacol. 104: 645–679.

    Article  Google Scholar 

  39. Malatynska, E., Wang, Y., Knapp, R. J., Santoro, G., Li, X., Waite, S., Roeske, W. R., and Yamamura, H. I. 1995. Human delta opioid receptor: a stable cell line for functional studies of opioids. Neuroreport. 6:613–616.

    Article  PubMed  CAS  Google Scholar 

  40. Law, P. Y., McGinn, T. M., Wick, M. J., Erikson, L. J., Evans, C., and Loh, H. H. 1994. Analysis of delta-opioid receptor activities stably expressed in CHO cell lines: function of receptor density? J. Pharmacol. and Exp. Therap. 271:1686–1694.

    CAS  Google Scholar 

  41. Kaufman, D. L., Keith Jr., D. E., Anton, B., Tian, J., Magendzo, K., Newman, D., Tran, T. H., Lee, D. S., Wen, C., Xia, Y., Lusis, A. J., and Evans, C. J. 1995. Characterization of the murine μ-opioid receptor gene. J. Biol. Chem. 270:15877–15883.

    Article  PubMed  CAS  Google Scholar 

  42. Zimprich, A., Simon, T., and Hollt, V. 1995. Cloning and expression of an isoform of the rat μ opioid receptor (rMOR1B) which differs in agonist induced desensitization from rMOR1. FEBS Lett. 359:142–146.

    Article  PubMed  CAS  Google Scholar 

  43. Baumhaker, Y., Gafini, M., Keren, O., and Sarne, Y. 1993. Selective and interactive down-regulation of μ- and δ-opioid receptors in human neuroblastoma SK-N-SH cells. Mol. Pharmacol. 44: 461–467.

    PubMed  CAS  Google Scholar 

  44. Seward, E., Hammond, C., and Henderson, G. 1991. Mu-opioidreceptor-mediated inhibition of the N-type calcium-channel current. Proc. R. Soc. Lond. [Biol]. 244:129–135.

    Article  CAS  Google Scholar 

  45. Toll, L. 1992. Comparison of mu opioid receptor binding on intact neuroblastoma cells with guinea pig brain and neuroblastoma cell membranes. J. Pharmacol. Exp. Therap. 260:9–15.

    CAS  Google Scholar 

  46. Werling, L. L., Puttfarcken, P. S., and Cox, B. M. 1988. Multiple agonist-affinity states of opioid receptors: regulation of binding by guanylyl nucleotides in guinea pig cortical, NG108-15 and 7315c cell membranes. Mol. Pharmacol. 33:423–431.

    PubMed  CAS  Google Scholar 

  47. Pert, C. B., and Snyder, S. H. 1974. Opiate receptor binding of agonists and antagonists affected differentially by sodium. Mol. Pharmacol. 10:868–879.

    CAS  Google Scholar 

  48. Law, P. Y., Hom, D. S., and Loh, H. H. 1985. Multiple affinity states of opiate receptor in neuroblastoma × glioma NG108-15 hybrid cells. J. Biol. Chem. 260:3561–3569.

    PubMed  CAS  Google Scholar 

  49. Toll, L., and Polgar, W. 1995. Receptor number mediates the agonist response of the mu receptor transfected into CHO cells. INRC Abstr. W54.

  50. Neer, E. J. 1995. Heterotrimeric G proteins: organizers of transmembrane signals. Cell. 80:249–257.

    Article  PubMed  CAS  Google Scholar 

  51. Paulssen, E. J., Paulssen, R. H., Haugen, T. B., Gautvik, K. M., and Gordeladze, J. O. 1991. Regulation of G protein mRNA levels by thyroliberin, vasoactive intestinal peptide and somatostatin in Prolactin-producing rat pituitary adenoma cells. Acta Physiol. Scand. 143:195–201.

    Article  PubMed  CAS  Google Scholar 

  52. Kleuss, C., Scherubl, H., Hescheler, J., Schultz, G., and Wittig, B. 1993. Selectivity in signal transduction determined by γ subunits of heterotrimeric G proteins. Science. 259:832–834.

    Article  PubMed  CAS  Google Scholar 

  53. Laugwitz, K. L., Offermanns, S., Spicher, K., and Schultz, G. 1993. μ- and δ-opioid receptors differentially couple to G protein subtypes in membranes of human neuroblastoma SHSY5Y cells. Neuron. 10:233–242.

    Article  PubMed  CAS  Google Scholar 

  54. Schroeder, J. E., Fischbach, P. S., Zheng, D., and McCleskey, E. W. 1991. Activation of mu opioid receptors inhibits transient high-and low-threshold Ca2+ currents, but spares a sustained current. Neuron 6:13–20.

    Article  PubMed  CAS  Google Scholar 

  55. Moises, H. C., Rusin, K. I., and Macdonald, R. L. 1994. μ- and κ-Opioid receptors selectively regulate the same transient components of high-threshold calcium current in rat dorsal root ganglion sensory neurons. J. Neurosci. 14:5903–5916.

    PubMed  CAS  Google Scholar 

  56. Rusin, K. I., and Moises, H. C. 1995. μ-Oploid receptor activation reduces multiple components of high-threshold calcium current in rat sensory neurons. J. Neurosci. 15:4315–4327.

    PubMed  CAS  Google Scholar 

  57. Rhim, H., and Miller, R. J. 1994. Oploid receptors modulate diverse types of calcium channels in the nucleus tractus solitarius of the rat. J. Neurosci. 14:7608–7615.

    PubMed  CAS  Google Scholar 

  58. Kasai, H. 1992. Vohage- and time-dependent inhibition of neuronal calcium channels by a GTP-binding protein in a mammalian cell line. J. Physiol. 448:189–209.

    PubMed  CAS  Google Scholar 

  59. Tallent, M., Dichter, M. A., Bell, G. I., and Reisine, T. 1994. The cloned kappa opioid receptor couples to an N-type calcium current in undifferentiated PC-12 cells. Neuroscience 63:1033–1040.

    Article  PubMed  CAS  Google Scholar 

  60. Morikawa, H., Fukuda, K., Kato, S., Mori, K., and Higashida, H. 1995. Coupling of the cloned μ-opioid receptor with the ω-conotoxin-sensitive Ca2+ current in NG108-15 cells. J. Neurochem. 65:1403–1406.

    Article  PubMed  CAS  Google Scholar 

  61. Kleppisch, T., Ahnert-Hilger, G., Gollasch, M., Spicher, K., Hescheler, J., Schultz, G., and Rosenthal, W. 1992. Inhibition of voltage-dependent Ca2+ channels via alpha 2-adrenergic and opioid receptors in cultured bovine adrenal chromaffin cells. Pfluegers Arch. 421:131–137.

    Article  CAS  Google Scholar 

  62. Xiao, R. P., Spurgeon, H. A., Capogrossi, M. C., and Lakatta, E. G. 1993. Stimulation of opioid receptors on cardiac ventricular myocytes reduces L-type Ca2+ channel current. J. Mol. Cell. Cardiol. 25:661–666.

    Article  PubMed  CAS  Google Scholar 

  63. Birnbaumer, L., Campbell, K. P., Catterall, W. A., Harpold, M. M., Hofmann, F., Horne, W. A., Mori, Y., Schwartz, A., Snutch, T. P., Tanabe, T., and Tsien, R. W. 1994. The naming of voltage-gated calcium channels. Neuron 13:505–506.

    Article  PubMed  CAS  Google Scholar 

  64. Bourinet, E., Soong, T. W., Stea, A., and Snutch, T. P. 1996. Determinants of the G protein-dependent opioid modulation of neuronal calcium channels. Proc. Natl. Acad. Sci. USA 93:1486–1491.

    Article  PubMed  CAS  Google Scholar 

  65. Simasko, S. M., Weiland, G. A., and Oswald, R. E. 1988. Pharmacological characterization of two calcium currents in GH3 cells. Am. J. Physiol. 254:E328-E336.

    PubMed  CAS  Google Scholar 

  66. Matteson, D. R., and Armstrong, C. M. 1986. Properties of two types of calcium channels in clonal pituitary cells. J. Gen. Physiol. 87:161–182.

    Article  PubMed  CAS  Google Scholar 

  67. Lievano, A., Bolden, A., and Horn, R. 1994. Calcium channels in excitable cells: divergent genotypic and phenotypic expression of alpha 1-subunits. Am. J. Physiol. 267:C411-C424.

    PubMed  CAS  Google Scholar 

  68. Hille, B. 1994. Modulation of ion-channel function by G-proteincoupled receptors. Trends Neurosci. 17:531–536.

    Article  PubMed  CAS  Google Scholar 

  69. Wilding, T. J., Womack, M. D., and McCleskey, E. W. 1995. Fast, local signal transduction between the μ opioid receptor and Ca2+ channels. J. Neurosci. 15:4124–4132.

    PubMed  CAS  Google Scholar 

  70. Bean, B. P. 1989. Neurotransmitter inhibition of neuronal calcium currents by changes in channel voltage dependence. Nature 340: 153–156.

    Article  PubMed  CAS  Google Scholar 

  71. Dolphin, A. C. 1996. Facilitation of Ca2+ current in excitable cells. Trends Neurosci. 19:35–43.

    Article  PubMed  CAS  Google Scholar 

  72. Tsunoo, A., Yoshii, M., and Narahashi, T. 1986. Block of calcium channels by enkephalin and somatostatin in neuroblastoma-glioma hybrid NG108-15 cells. Proc. Natl. Acad. Sci. USA 83:9832–9836.

    Article  PubMed  CAS  Google Scholar 

  73. Grassi, F., and Lux, H. D. 1989. Voltage-dependent GABA-induced modulation of calcium currents in chick sensory neurons. Neurosci. Let. 105:113–119.

    Article  CAS  Google Scholar 

  74. Keja, J. A., and Kits, K. S. 1994. Voltage dependence of G-protein-mediated inhibition of high-voltage-activated calcium channels in rat pituitary melanotropes. Neurosci. 62:281–289.

    Article  CAS  Google Scholar 

  75. Hescheler, J., and Schultz, G. 1993. G-proteins involved in the calcium channel signaling system. Curr. Opin. Neurobiol. 3:360–367.

    Article  PubMed  CAS  Google Scholar 

  76. Wickman, K. D., and Clapham, D. E. 1995. G-protein regulation of ion channels. Curr. Opin. Neurobiol. 5:278–285.

    Article  PubMed  CAS  Google Scholar 

  77. Dolphin, A. C. 1995. The G. L. Brown Prize Lecture. Voltagedependent calcium channels and their modulation by neurotransmitters and G proteins. Expl. Physiol. 80:1–36.

    CAS  Google Scholar 

  78. Clapham, D. E., and Neer, E. J. 1993. New roles for G-protein beta gamma-dimers in transmembrane signaling. Nature. 365:403–406.

    Article  PubMed  CAS  Google Scholar 

  79. Muller, S., and Lohse, M. J. 1995. The role of G-protein beta gamma subunit in signal transduction. Biochem. Soc. Transact. 23:141–148.

    CAS  Google Scholar 

  80. Ikeda, S. R. 1996. Voltage-dependent modulation of N-type calcium channels by G-protein βγ subunits. Nature. 380:255–258.

    Article  PubMed  CAS  Google Scholar 

  81. Herlitze, S., Garcia, D. E., Mackie, K., Hille, B., Scheuer, T., and Catterall, W. A. 1996. Modulation of Ca2+ channels by G-protein βγ subunits. Nature. 380:258–262.

    Article  PubMed  CAS  Google Scholar 

  82. Schonbrunn, A. 1990. Somatostatin action in pituitary cells involves two independent transduction mechanisms. Metabolism. 39:96–100.

    Article  PubMed  CAS  Google Scholar 

  83. Taussig, R., Sanchez, S., Rifo, M., Gilman, A. G., and Belardetti, F. 1992. Inhibition of the omega-conotoxin-sensitive calcium current by distinct G proteins. Neuron. 8:799–809.

    Article  PubMed  CAS  Google Scholar 

  84. Piros, E. T., Marounian, C. E., Hales, T. G., and Evans, C. J. 1996. Cloned μ- and δ-opioid receptors inhibit prolactin secretion from transfected GH3 cells. Soc. Neurosci. Abstr. In press.

  85. Schoffelmeer, A. N. M., Wierenga, E. A., and Mulder, A. H. 1986. Role of adenylate cyclase in presynaptic α2-adrenoreceptor and μ-opioid receptor-mediated inhibition of [3H]noradrenaline release from rat brain cortex slices. J. Neurochem. 46:1711–1717.

    Article  PubMed  CAS  Google Scholar 

  86. Robinson, I. M., Finnegan, J. M., Monck, J. R., Wightman, R. M., and Fernandez, J. M. 1995. Colocalization of calcium entry and exocytotic release sites in adrenal chromaffin cells. Proc. Natl. Acad. Sci. USA. 92:2474–2478.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, 90095, Los Angeles, CA

    Elemer T. Piros & Chris J. Evans

  2. School of Medicine, Brain Research Institute University of California, Los Angeles, 90095, Los Angeles, CA

    Elemer T. Piros, Tim G. Hales Ph.D. & Chris J. Evans

  3. Dept. of Anesthesiology, School of Medicine, UCLA, 90095-1778, Los Angeles, CA

    Tim G. Hales Ph.D.

Authors
  1. Elemer T. Piros
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tim G. Hales Ph.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chris J. Evans
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Special issue dedicated to Dr. Eric J. Simon.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Piros, E.T., Hales, T.G. & Evans, C.J. Functional analysis of cloned opioid receptors in transfected cell lines. Neurochem Res 21, 1277–1285 (1996). https://doi.org/10.1007/BF02532368

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02532368

Key words

Search

Navigation