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Regulation of Opioid Receptors

  • Chapter
The Opiate Receptors

Part of the book series: The Receptors ((REC))

Abstract

Two processes by which the response of cells to hormones and transmitters is modulated are (1) regulation of the number of cellular receptors or (2) regulation of their sensitivity to applied ligand. The opioid receptors have been found to exhibit both types of modulation. In some systems, chronic treatment with opioid ligands results in alterations in the number of cell surface receptors; receptor numbers are decreased on treatment with agonists and increased on antagonist treatment. Additionally, both ligand affinity and receptor coupling to effector systems can be modulated by agents such as cations and guanyl nucleotides.

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References

  • Abood, M. E., Hurley, J. B., Pappone, M.-C., Bourne, H. R., and Stryer, L. (1982) Functional homology between signal-coupling proteins: Cholera toxin inactivates the GTPase activity of transducin. J. Biol. Chem. 257, 10540–10543.

    PubMed  CAS  Google Scholar 

  • Bardo, M. T., Bhatnagar, R. K., and Gebhart, G. F. (1982) Differential effects of chronic morphine and naloxone on opiate receptors, monoamines, and morphine-induced behaviors in preweanling rats. Dev. Brain Res. 4, 139–147.

    Article  CAS  Google Scholar 

  • Bennett, D. B., Spain, J. W., Laskowski, M. B., Roth, B. L., and Coscia, C. J. (1985) Stereospecific opiate-binding sites occur in coated vesicles. J. Neurosci. 5, 3010–3015.

    PubMed  CAS  Google Scholar 

  • Blanchard, S. G., Chang, K.-J., and Cuatrecasas, P. (1982) Studies on the mechanism of enkephalin receptor down regulation. Life Sci. 31, 1311–1314.

    Article  PubMed  CAS  Google Scholar 

  • Blanchard, S. G., Chang, K.-J., and Cuatrecasas, P. (1983) Characterization of the association of tritiated enkephalin with neuroblastoma cells under conditions optimal for receptor down regulation. J. Biol. Chem. 258, 1092–1097.

    PubMed  CAS  Google Scholar 

  • Blanchard, S. G., Chang, K.-J., and Cuatrecasas, P. (1984) Visualization of enkephalin receptors by image-intensified fluorescence microscopy. Meth. Enzymol. 103, 219–227.

    Article  Google Scholar 

  • Blume, A. J. (1978) Interaction of ligands with the opiate receptors of brain membranes: Regulation by ions and nucleotides. Proc. Natl. Acad. Sci. USA 75, 1713–1717.

    Article  PubMed  CAS  Google Scholar 

  • Blume, A. J., Lichtshtein, D., and Boone, G. (1979) Coupling of opiate receptors to adenylate cyclase: Requirement for Na ± and GTP. Proc. Natl. Acad. Sci. USA 76, 5626–5630.

    Article  PubMed  CAS  Google Scholar 

  • Bokoch, G. M., Katada, T., Northup, J. K., Hewlett, E. L., and Gilman, A. G. (1983) Identification of the predominant substrate for ADP-ribosylation by islet activating protein. J. Biol. Chem. 258, 2072–2075.

    PubMed  CAS  Google Scholar 

  • Bokoch, G. M., Katada, T., Northup, J. K., Ui, M., and Gilman, A. G. (1984) Purification and properties of the inhibitory guanine nucleotide-binding regulatory component of adenylate cyclase. J. Biol. Chem. 259, 3560–3567.

    PubMed  CAS  Google Scholar 

  • Brown, M. S., Anderson, R. G. W., and Goldstein, J. L. (1983) Recyling receptors: The round-trip itinerary of migrant membrane proteins. Cell 32, 663–667.

    Article  PubMed  CAS  Google Scholar 

  • Burns, D. L., Hewlett, E. L., Moss, J., and Vaughan, M. (1983) Pertussis toxin inhibits enkephalin stimulation of GTPase of NG108–15 cells. J. Biol. Chem. 258, 1435–1438.

    PubMed  CAS  Google Scholar 

  • Cassel, D. and Pfeuffer, T. (1978) Mechanism of cholera toxin action: Covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. Proc. Natl. Acad. Sci. USA 75, 2669–2673.

    Article  PubMed  CAS  Google Scholar 

  • Chang, K.-J. and Cuatrecasas, P. (1979) Multiple opiate receptors: Enkephalins and morphine bind to receptors of different specificity. J. Biol. Chem. 254, 2610–2618.

    PubMed  CAS  Google Scholar 

  • Chang, K.-J., Miller, R. J., and Cuatrecasas, P. (1978) Interaction of enkephalin with opiate receptors in intact cultured cells. Mol. Pharmacol. 14, 961–970.

    PubMed  CAS  Google Scholar 

  • Chang, K.-J., Hazum, E., Killian, A., and Cuatrecasas, P. (1981) Interactions of ligands with morphine and enkephalin receptors are differentially affected by guanine nucleotide. Mol. Pharmacol. 20, 1–7.

    PubMed  CAS  Google Scholar 

  • Chang, K.-J., Eckel, R. W., and Blanchard, S. G. (1982) Opioid peptides induce reduction of enkephalin receptors in cultured neuroblastoma cells. Nature 296, 446–448.

    Article  PubMed  CAS  Google Scholar 

  • Chang, K.-J., Blanchard, S. G., and Cuatrecasas, P. (1983) Unmasking of magnesium-dependent high-affinity binding sites for [D-Ala2, D-Leus)enkephalin after pretreatment of brain membranes with guanine nucleotides. Proc. Natl. Acad. Sci. USA 80, 940–944.

    Article  PubMed  CAS  Google Scholar 

  • Childers, S. R. and Snyder, S. H. (1980) Differential regulation by guanine nucleotides of opiate agonist and antagonist receptor interactions. J. Neurochem. 34, 583–593.

    Article  PubMed  CAS  Google Scholar 

  • Codina, J., Hildebrandt, J., Iyengar, R., Birnbaumer, L., Sekura, R. D., and Manclark, C. R. (1983) Pertussis toxin substrate, the putative N, component of adenylyl cyclases, is an aß heterodimer regulated by guanine nucleotide and magnesium. Proc. Natl. Acad. Sci. USA 80, 4276–4280.

    Article  PubMed  CAS  Google Scholar 

  • Codina, J., Hildebrandt, J. D., Birnbaumer, L., and Sekura, R. D. (1984) Effects of guanine nucleotides and Mg on human erythrocyte N and N5, the regulatory components of adenylyl cyclase. J. Biol. Chem. 259, 11408–11418.

    PubMed  CAS  Google Scholar 

  • Costa, T., Aktories, K., Schultz, G., and Wuster, M. (1983) Pertussis toxin decreases opiate receptor binding and adenylate inhibition in a neuro-blastoma x glioma hybrid cell line. Life Sci. 33 (suppl. 1), 219–222.

    Article  PubMed  CAS  Google Scholar 

  • Costa, T., Wuster, M., Gramsch, C., and Herz, A. (1985) Multiple states of opioid receptors may modulate adenylate cyclase in intact neuroblastoma x glioma hybrid cells. Mol. Pharmacol. 28, 146–154.

    PubMed  CAS  Google Scholar 

  • Cote, T. E., Frey, E. A., and Sekura, R. D. (1984) Altered activity of the inhibitory guanyl nucleotide-binding component (Ni) induced by pertussis toxin: Uncoupling of N, from receptor with continued coupling of N, to the catalytic unit. J. Biol. Chem. 259, 8693–8698.

    PubMed  CAS  Google Scholar 

  • Dingledine, R., Valentino, R. J., Bostock, E., King, M. E., and Chang, K.-J. (1983) Down-regulation of 8 but not µ opioid receptors in the hippocampal slice associated with loss of physiological response. Life Sci. 33 (suppl. 1), 333–336.

    Article  PubMed  CAS  Google Scholar 

  • Florio, V. A. and Sternweis, P. C. (1985) Reconstitution of resolved muscarinic cholinergic receptors with purified GTP-binding proteins. J. Biol. Chem. 260, 3477–3483.

    PubMed  CAS  Google Scholar 

  • Frances, B., Moisand, C., and Meunier, J.-C. (1985) Na + ions and Gpp(NH)p selectively inhibit agonist interactions at µµ- and K-opioid receptor sites in rabbit and guinea-pig cerebellum membranes. Eur. J. Pharmacol. 117, 223–232.

    Article  PubMed  CAS  Google Scholar 

  • Gardner, E. L., Zukin, R. S., and Makman, M. H. (1980) Modulation of opiate receptor binding in striatum and amygdala by selective mesencephalic lesions. Brain Res. 194, 232–239.

    Article  PubMed  CAS  Google Scholar 

  • Gilman, A. G. (1984a) Guanine nucleotide-binding regulatory proteins and dual control of adenylate cyclase. J. Clin. Invest. 73, 1–4.

    Article  PubMed  CAS  Google Scholar 

  • Gilman, A. G. (1984b) G proteins and dual control of adenylate cyclase. Cell 36, 577–579.

    Article  PubMed  CAS  Google Scholar 

  • Gill, D. M. and Meren, R. (1978) ADP-ribosylation of membrane proteins catalyzed by cholera toxin: Basis of the activation of adenylate cyclase. Proc. Natl. Acad. Sci. USA 75, 3050–3054.

    Article  PubMed  CAS  Google Scholar 

  • Gwynn, G. J. and Costa, E. (1982) Opioids regulate cGMP formation in cloned neuroblastoma cells. Proc. Natl. Acad. Sci. USA 79, 690–694.

    Article  PubMed  CAS  Google Scholar 

  • Haga, K., Haga, T., Ichiyama, A., Katada, T., Kurose, H., and Ui, M. (1985) Functional reconstitution of purified muscarinic receptors and inhibitory guanine nucleotide regulatory protein. Nature 316, 731–733.

    Article  PubMed  CAS  Google Scholar 

  • Hazum, E., Chang, K.-J., and Cuatrecasas, P. (1979a) Opiate (enkephalin) receptors of neuroblastoma cells: Occurrence in clusters on the cell surface. Science 206, 1077–1079.

    Article  PubMed  CAS  Google Scholar 

  • Hazum, E., Chang, K.-J., and Cuatrecasas, P. (1979b) Role of disulphide and sulphydryl groups in clustering of enkephalin receptors in neuro-blastoma cells. Nature 282, 626–628.

    Article  PubMed  CAS  Google Scholar 

  • Hazum, E., Chang, K.-J., and Cuatrecasas, P. (1980) Cluster formation of opiate (enkephalin) receptors in neuroblastoma cells: Differences between agonists and antagonists and possible relationships to biological functions. Proc. Natl. Acad. Sci. USA 77, 3038–3041.

    Article  PubMed  CAS  Google Scholar 

  • Hazum, E., Chang, K.-J., and Cuatrecasas, P. (1981) Receptor redistribution induced by hormones and neurotransmitters: Possible relationships to biological functions. Neuropeptides 1, 217–230.

    Article  CAS  Google Scholar 

  • Hildebrandt, J. D., Sekura, R. D., Codina, J., Iyengar, R., Manclark, C. R., and Birnbaumer, L. (1983) Stimulation and inhibition of adenylyl cyclases mediated by distinct regulatory proteins. Nature 302, 706–709.

    Article  PubMed  CAS  Google Scholar 

  • Hitzemann, R. J., Hitzemann, B. A., and Loh, H. H. (1974) Binding of 3H-naloxone in the mouse brain: Effect of ions and tolerance development. Life Sci. 14, 2393–2404.

    Article  PubMed  CAS  Google Scholar 

  • Hollt, V., Dum, J., Blasig, J., Schubert, P., and Herz, A. (1975) Comparison of in vivo and in vitro parameters of opiate receptor binding in naive and tolerant/dependent rodents. Life Sci. 16, 1823–1828.

    Article  PubMed  CAS  Google Scholar 

  • Hsia, J. A., Moss, J., Hewlett, E. L., and Vaughan, M. (1984) ADP-ribosylation of adenylate cyclase by pertussis toxin: Effects on inhibitory agonist binding. J. Biol. Chem. 259, 1086–1090.

    PubMed  CAS  Google Scholar 

  • Katada, T. and Ui, M. (1982) ADP ribosylation of the specific membrane protein of C6 cells by islet-activating protein associated with modification of adenylate cyclase activity. J. Biol. Chem. 257, 7210–7216.

    PubMed  CAS  Google Scholar 

  • King, A. C. and Cuatrecasas, P. (1981) Peptide hormone-induced receptor mobility, aggregation and internalization. N. Eng. J. Med. 305, 77–88.

    Article  CAS  Google Scholar 

  • Klee, W. A. and Nirenberg, M. (1976) Mode of action of endogenous opiate peptides. Nature 263, 609–612.

    Article  PubMed  CAS  Google Scholar 

  • Klee, W. A. and Streaty, R. A. (1974) Narcotic receptor sites in morphine-dependent rats. Nature 248, 61–63.

    Article  PubMed  CAS  Google Scholar 

  • Koski, G. and Klee, W. A. (1981) Opiates inhibit adenylate cyclase by stimulating GTP hydrolysis. Proc. Natl. Acad. Sci. USA 78, 4185–4189.

    Article  PubMed  CAS  Google Scholar 

  • Kurose, H., Katada, T., Amano, T., and Ui, M. (1983) Specific uncoupling by islet-activating protein, pertussis toxin, of negative signal transduction via a-adrenergic, cholinergie, and opiate receptors in neuroblastoma x glioma hybrid cells. J. Biol. Chem. 258, 4870–4875.

    PubMed  CAS  Google Scholar 

  • Lahti, R. A. and Collins, R. J. (1978) Chronic naloxone results in prolonged increases in opiate binding sites in brain. Eur. J. Pharmacol. 51, 185–186.

    Article  PubMed  CAS  Google Scholar 

  • Lampert, A., Nirenberg, M., and Klee, W. A. (1976) Tolerance and dependence evoked by an endogenous opiate peptide. Proc. Natl. Acad. Sci. USA 73, 3165–3167.

    Article  PubMed  CAS  Google Scholar 

  • Law, P.-Y., Horn, D. S., and Loh, H. H. (1982) Loss of opiate receptor activity in neuroblastoma x glioma NG108–15 hybrid cells after chronic opiate treatment: A multiple-step process. Mol. Pharmacol. 22, 1–4.

    PubMed  CAS  Google Scholar 

  • Law, P.-Y., Horn, D. S., and Loh, H. H. (1983a) Opiate receptor down-regulation and desensitization in neuroblastoma x glioma NG108–15 hybrid cells are two separate cellular adaptation processes. Mol. Pharmacol. 24, 413–424.

    PubMed  CAS  Google Scholar 

  • Law, P.-Y., Hom, D. S., and Loh, H. H. (1983b) Opiate regulation of adenosine 3’:5-cyclic monphosphate level in neuroblastoma x glioma NG108–15 hybrid cells: Relationship between receptor occupancy and effect. Mol. Pharmacol. 23, 26–35.

    PubMed  CAS  Google Scholar 

  • Law, P.-Y., Horn, D. S., and Loh, H. H. (1984) Down-regulation of opiate receptor in neuroblastoma x glioma NG108–15 cells: Chloroquine promotes accumulation of tritiated enkephalin in the lysosomes. J. Biol. Chem. 259, 4096–4104.

    PubMed  CAS  Google Scholar 

  • Law, P.-Y., Hom, D. S., and Loh, H. H. (1985a) Multiple affinity states of opiate receptor in neuroblastoma x glioma NG108–15 hybrid cells: Opiate agonist association rate is a function of receptor occupancy. J. Biol. Chem. 260, 3561–3569.

    PubMed  CAS  Google Scholar 

  • Law, P.-Y., Lovie, A. K., and Loh, H. H. (1985b) Effect of pertussis toxin treatment on the down-regulation of opiate receptors in neuroblastoma x glioma NG108–15 hybrid cells. J. Biol. Chem. 260, 14818–14823.

    PubMed  CAS  Google Scholar 

  • Lenoir, D., Barg, J., and Simantov, R. (1983) Down-regulation of opiate receptors in serum-free cultures of aggregating fetal brain cells. Life Sci. 33 (suppl. 1), 337–340.

    Article  PubMed  CAS  Google Scholar 

  • Malbon, C. C., Mangano, T. J., and Watkins, D. C. (1985) Heart contains two substrates (M, = 40,000 and 41,000) for pertussis toxin-catalyzed ADP-ribosylation that co-purify with N. Biochem. Biophys. Res. Comm. 128, 809–815.

    Article  CAS  Google Scholar 

  • Manning, D. R., Fraser, B. A., Kahn, R. A., and Gilman, A. G. (1984) ADPribosylation of transducin by islet-activating protein: Identification of asparagine as the site of ADP-ribosylation. J. Biol. Chem. 259, 749–756.

    PubMed  CAS  Google Scholar 

  • Milligan, G. and Klee, W. A. (1985) The inhibitory guanine nucleotide-binding protein (Ni) purified from bovine brain is a high affinity GTPase. J. Biol. Chem. 260, 2057–2063.

    PubMed  CAS  Google Scholar 

  • Moudy, A. M., Spain, J. W., and Coscia, C. J. (1985) Differential up-regulation of microsomal and synaptic membrane si-receptors. Biochem. Biophys. Res. Comm. 132, 735–741.

    Article  PubMed  CAS  Google Scholar 

  • Nakata, Y., Chang, K.-J., Mitchell, C. L., and Hong, J. S. (1985) Repeated electroconvulsive shock down regulates the opioid receptors in rat brain. Brain Res. 346, 160–163.

    Article  PubMed  CAS  Google Scholar 

  • Neer, E. J., Lok, J. M., and Wolf, L. G. (1984) Purification and properties of the inhibitory guanine nucleotide regulatory unit of brain adenylate cyclase. J. Biol. Chem. 259, 14222–14229.

    PubMed  CAS  Google Scholar 

  • Northup, J. K., Sternweis, P. C., Smigel, M. D., Schleifer, L. S., Ross, E. M., and Gilman, A. G. (1980) Purification of the regulatory component of adenylate cyclase. Proc. Natl. Acad. Sci. USA 77, 6516–6520.

    Article  PubMed  CAS  Google Scholar 

  • Pastan, I. and Willingham, M. C. (1983) Receptor-mediated endocytosis: Coated pits, receptosomes and the golgi. TIBS 8, 250–254.

    CAS  Google Scholar 

  • Pasternak, G. W., Snowman, A. M., and Snyder, S. H. (1975) Selective enhancement of [3H]opiate agonist binding by divalent cations. Mol. Pharmacol. 11, 735–744.

    PubMed  CAS  Google Scholar 

  • 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 

  • Pert, C. B., Pasternak, G. W., and Snyder, S. H. (1973) Opiate agonists and antagonists discriminated by receptor binding in brain. Science 182, 1359–1361.

    Article  PubMed  CAS  Google Scholar 

  • Roth, B. L., Laskowski, M. B., and Coscia, C. J. (1981) Evidence for distinct subcellular sites of opiate receptors: Demonstration of opiate receptors in smooth microsomal fractions isolated from rat brain. J. Biol. Chem. 256, 10117–10123.

    CAS  Google Scholar 

  • Schulz, R., Wuster, M., and Herz, A. (1979) Supersensitivity to opioids following chronic blockade of endorphin activity by naloxone. Naunyn Schmiedebergs Arch. Pharmacol. 306, 93–96.

    Article  PubMed  CAS  Google Scholar 

  • Sharma, S. K., Klee, W. A., and Nirenberg, M. (1975) Dual regulation of adenylate cyclase accounts for narcotic dependence and tolerance. Proc. Natl. Acad. Sci. USA 72, 3092–3096.

    Article  PubMed  CAS  Google Scholar 

  • Simantov, R., Levy, R., and Baram, D. (1982) Down regulation of enkephalin (8) receptors: Demonstration in membrane bound and solubilized receptors. Biochim. Biophys. Acta. 721, 478–484.

    Article  PubMed  CAS  Google Scholar 

  • Simon, E. J. and Groth, J. (1975) Kinetics of opiate inactivation by sulfhydryl reagents: Evidence for a conformational change in the presence of sodium ions. Proc. Natl. Acad. Sci. USA 72, 2404–2407.

    Article  PubMed  CAS  Google Scholar 

  • Simon, E. J. and Hiller, J. M. (1978) In vitro studies on opiate receptors and their ligands. Fed. Proc. 37, 141–146.

    CAS  Google Scholar 

  • Sternweis, P. C. and Robishaw, J. D. (1984) Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain. J. Biol. Chem. 259, 13806–13813.

    PubMed  CAS  Google Scholar 

  • Sunyer, T., Codina, J., and Birnbaumer, L. (1984) GTP hydrolysis by pure Ni, the inhibitory regulatory component of adenylyl cyclases. J. Biol. Chem. 259, 15447–15451.

    PubMed  CAS  Google Scholar 

  • Tang, A. H. and Collins, R. J. (1978) Enhanced analgesic effects of morphine after chronic administration of naloxone in the rat. Eur. J. Pharmacol. 47, 473–474.

    Article  PubMed  CAS  Google Scholar 

  • Tempel, A., Crain, S., Simon, E. J., and Zukin, R. S. (1983) Opiate receptor upregulation in explants of spinal cord-dorsal root ganglia. Soc. Neuro-sci. Abst. 9, 327.

    Google Scholar 

  • Tempel, A., Gardner, E. L., and Zukin, R. S. (1984) Visualization of opiate receptor upregulation by light microscopic autoradiography. Proc. Natl. Acad. Sci. USA 81, 3893–3897.

    Article  PubMed  CAS  Google Scholar 

  • Zidovetski, R., Yarden, Y., Schlessinger, J., and Jovin, T. M. (1981) Rotational diffusion of epidermal growth factor complexed to cell surface receptors reflects rapid microaggregation and endocytosis of occupied receptors. Proc. Natl. Acad. Sci. USA 78, 6981–6985.

    Article  Google Scholar 

  • Zukin, R. S., Sugarman, J. R., Fitz-Syage, M. L., Gardner, E. L., Zukin, S. R., and Gintzler, A. R. (1982) Naltrexone-induced opiate receptor supersensitivity. Brain Res. 245, 285–292.

    Article  PubMed  CAS  Google Scholar 

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Authors
  1. Steven G. Blanchard
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  2. Kwen-Jen Chang
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Editors and Affiliations

  1. Memorial Sloan-Kettering Cancer Center and Cornell University Medical College, New York, New York, USA

    Gavril W. Pasternak

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Blanchard, S.G., Chang, KJ. (1988). Regulation of Opioid Receptors. In: Pasternak, G.W. (eds) The Opiate Receptors. The Receptors. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-60761-990-1_12

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  • DOI: https://doi.org/10.1007/978-1-60761-990-1_12

  • Publisher Name: Humana Press, Totowa, NJ

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