Summary
We have utilized the technique of in vitro autoradiography to ascertain that opioid receptors are transported in the rat vagus nerve and in the rat dorsal spinal root fibers. In the dorsal roots, opioid receptors accumulated on both sides of the ligatures. In the vagus nerve, a distal accumulation of binding sites was difficult to detect, however, proximal to the ligatures, vagal receptors accumulated in a linear fashion during the first 12 h of ligation. At longer periods after ligation, accumulation was less than expected and the receptors appeared to migrate retrogradely. The receptor transport could be blocked by intravagal colchicine injection and the receptor translocation could be elicited in isolated vagal nerve segments suggesting that the receptors move by fast transport. Sodium chloride, present in the incubation medium, inhibited [3H]dihydromorphine ([3H]DHM) binding to receptors adjacent to and far from the proximal aspect of the ligature with IC50's of 42 mM and 51 mM, respectively. The addition of GTP in the incubation medium also inhibited [3H]DHM binding to “proximal’ and “far proximal” receptors with IC50's of 0.27 μM and 1.0 μM, respectively. The presence of GTP also inhibited [3H]naloxone ([3H]Nal) binding to “proximal” and “far proximal” receptors with IC50's of 0.34 μM and 0.66 μM, respectively. The transported vagal opioid receptors bound the ligands in a stereospecific manner. Using [3H]DHM, [3H]D-ala2-D-leu5-enkephalin ([3H]DADL), and [3H]ethylketocyclazocine ([3H]EKC), we found that most of the transported vagal receptors have mupharmacology although kappa and delta receptors are present.
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References
Alonso FG, Gena V, Garcia AG, Kirpekar SM, Sanchez-Garcia P (1982) Presence and axonal transport of cholinoceptor, but not adrenoceptor sites on a cat noradrenergic neuron. J Physiol 333:595–618
Atweh SF, Murrin LC, Kuhar MJ (1978) Presynaptic localization of opiate receptors in the vagal and accessory optic systems: an autoradiographic study. Neuropharmacology 17:65–71
Basbaum AI, Fields HL (1984) Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Ann Rev Neurosci 7:309–338
Bidlack JM, Abood LG, Osei-Gyimah P, Archer S (1981) Purification of the opiate receptor from rat brain. Proc Natl Acad Sci USA 78:636–639
Bisby MA (1987) Does recycling have functions other than disposal? In: Smith RS, Bisby MA (eds) Axonal transport. Alan R Liss, New York, pp 365–383
Chang K-J, Cooper BR, Hazum E, Cuatrecasas P (1979) Multiple opiate receptors: different regional distribution in the brain and differential binding of opiates and opioid peptides. Mol Pharmacol 16:91–104
Chang K-J, Cuatrecasas P (1979) Multiple opiate receptors: enkephalins and morphine bind to receptors of different specificity. J Biol Chem 254:2610–2618
Chang K-J, Hazum E, Killian A, Cuatrecasas P (1981a) Interactions of ligands with morphine and enkephalin receptors are differentially affected by guanine nucleotide. Mol Pharmacol 20:1–7
Chang K-J, Hazum E, Cuatrecasas P (1981b) Novel opiate binding sites selective for benzomorphan drugs. Proc Natl Acad Sci USA 78:4141–4145
Childers SR, Snyder SH (1980) Differential regulation by guanine nucleotides of opiate agonist and antagonist receptor interactions. J Neurochem 34:583–593
Chow T, Zukin RS (1983) Solubilization and preliminary characterization of mu and kappa opiate receptor subtypes from rat brain. Mol Pharmacol 24:203–212
Dawson TM, Gehlert DR, Snowhill EW, Wamsley JK (1985) Quantitative autoradiographic evidence for axonal transport of imipramine receptors in the CNS. Neurosci Lett 55:261–266
Dolphin AC, (1987) Nucleotide binding proteins in signal transduction and disease. Trends Neurosci 10:53–57
Fields HL, Emson PC, Leigh BK, Gilbert RFT, Iversen LL (1980) Multiple opiate receptor sites on primary afferent fibres. Nature 284:351–353
Gioannini T, Foucaud B, Hiller JM, Hatten ME, Simon EJ (1982) Lectin binding of solubilized opiate receptors: evidence for their glycoprotein nature. Biochem Biophys Res Commun 105:1128–1134
Goodman RR, Snyder SH (1982) Kappa receptors localized by autoradiography to deep layers of cerebral cortex: relation to sedative effects. Proc Natl Acad Sci USA 79:5703–5707
Goodman RR, Pasternak GW (1984) Multiple opiate receptors. In: Kuhar M, Pasternak GW (eds) Analgesics: neurochemical, behavioral and clinical perspectives. Raven Press, New York, pp 69–96
Grafstein B, Forman DS (1980) Intracellular transport in neurons. Phys Rev 60:1167–1283
Hammerschlag R, Stone GC (1982) Membrane delivery by fast axonal transport. Trends Neurosci 5:12–15
Hollenbeck PJ (1989) The transport and assembly of the axonal cytoskeleton. J Cell Biol 108:223–227
Holtzman E, Mercurio AM (1980) Membrane circulation in neurons and photoreceptors: some unresolved issues. In: Bourne CH, Danielli JF (eds) International review of cytology. Academic Press, New York, pp 1–67
Howells RD, Gioannini TL, Hiller JM, Simon EJ (1982) Solubilization and characterization of active opiate binding sites from mammalian brain. J Pharmacol Exp Ther 222:629–634
Koski G, Simonds WF, Klee WA (1981) Guanine nucleotides inhibit binding of agonists and antagonists to soluble opiate receptors. J Biol Chem 256:1536–1538
Kuhar MJ (1985) Receptor localization with the microscope. In: Yamamura HI, Enna SJ, Kuhar MJ (eds) Neurotransmitter receptor binding. New York
Kuhar MJ, DeSouza EB, Unnerstall JK (1986) Neurotransmitter mapping by autoradiography and other methods. Ann Rev Neurosci 9:27–59
Laduron P (1980) Axoplasmic transport of muscarinic receptors. Nature 286:287–288
Laduron PM (1987a) Axonal transport of neuroreceptors: possible involvement in long-term memory. Neuroscience 22:767–779
Laduron (1987b) Axonal transport of presynaptic receptors. In: Smith RS, Bisby MA (eds) Axonal transport. Alan R Liss, New York, pp 347–363
Lasek RJ, Brady ST (1982) The structural hypothesis of axonal transport: two classes of moving elements. In: Weiss D (ed) Axonal transport. Springer, Berlin, pp 397–405
Lees GM, Kosterlitz HW, Waterfield (1972) Characteristics of morphine-sensitive release of neurotransmitter substances. In: Kosterlitz HW, Collier HOJ, Villareal JE (eds) Agonist and antagonist actions of narcotic analgesic drugs. Macmillan, London Basingstoke, pp 142–152
Levin BE (1982) Presynaptic localization and axonal transport of beta-1 adrenoreceptors in the rat brain. Science 217:555–557
Levin BE (1984) Axonal transport and presynaptic location of alpha-2 adrenoreceptors in locus coeruleus neurons. Brain Res 321:180–182
Lewis SJ, Cincotta M, Verberne AJ, Jarrott B, Lodge D, Beart PM (1987) Receptor autoradiography with [3H]L-glutamate reveals the presence and axonal transport of glutamate receptors in vagal afferent neurons of the rat. Eur J Pharmacol 144:413–415
Lundberg JM, Hokfelt T, Nilsson G, Terenius L, Rehfeld J, Elde R, Said S (1978) Peptide neurons in the vagus, splanchnic and sciatic nerves. Acta Physiol Scand 104:499–501
Lundberg JM, Hokfelt T, Kewenter J, Pettersson G, Ahlman H, Edin R, Dahlstrom A, Nilsson G, Terenius L, Wallensten K, Said S (1979) Substance P-, VIP and enkephalin-like immuno reactivity in the human vagus nerve. Gastroenterology 77:468–471
McClure WO (1972) Effect of drugs upon axoplasmis transport. Adv Pharmacol Chemother 10:185–220
Millington WR, Aizenman E, Bierkamper GG, Zarbin MA, Kuhar MJ (1985) Axonal transport of alpha-bungarotoxin binding sites in rat sciatic nerve. Brain Res 340:269–276
Ninkovic M, Hunt SP (1983) Alpha-bungarotoxin binding sites on sensory neurons and their axonal transport in sensory afferents. Brain Res 272:57–69
North RA (1979) Opiates, Opioid peptides and single neurons. Life Sci 24:1527–1546
Nixon RA (1987) The axonal transport of cytoskeletal proteins: a reappraisal. In: Smith R, Bisby M (eds) Axonal transport. Alan R Liss, New York, pp 175–200
Ochs S (1982) Axoplasmic transport and its relation to other nerve functions. John Wiley & Sons, New York
Roth BL, Laskowski MB, Coscia CJ (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
Schnapp BJ, Reese TS (1986) New developments in understanding rapid axonal transport. Trends Neurosci 9:155–162
Shefner SA, North RA, Zukin RS (1981) Opiate effects on rabbit vagus nerve: electrophysiology and radioligand binding. Brain Res 221:109–116
Snowhill EW, Wamsley JK (1983) Serotonin type-2 receptors undergo axonal transport in the medial forebrain bundle. Eur J Pharmacol 95:325–327
Starke K (1977) Regulation of noradrenaline release by presynaptic receptor systems. Rev Physiol Biochem Pharmacol 77:1–124
Wamsley JK (1983a) Muscarinic cholinergic receptors undergo axonal transport in the brain. Eur J Pharmacol 86:309–310
Wamsley JK (1983b) Opioid receptors: autoradiography. Pharmacol Rev 35:69–83
Wamsley JK, Palacios JM (1983) Apposition techniques of autoradiography for microscopic receptor localization. In: Barker JL, McKelvy JF (eds) Current methods in cellular neurobiology. John Wiley and Sons, New York, pp 241–268
Young WS III, Wamsley JK, Zarbin MA, Kuhar MJ (1980) Opioid receptors undergo axonal flow. Science 210:76–78
Zarbin MA, Wamsley JK, Innis RB, Kuhar MJ (1981) Cholecys tokinin receptors: presence and axonal flow in the rat vagus nerve. Life Sci 29:697–705
Zarbin MA, Wamsley JK, Kuhar MJ (1982a) Axonal transport of muscarinic cholinergic receptors in rat vagus nerve: high and low affinity agonist receptors move in opposite directions and differ in nucleotide sensitivity. J Neurosci 2:934–941
Zarbin MA, Wamsley JK, Kuhar MJ (1982b) Peptide receptors undergo axonal transport in the rat vagus nerve. In: Costa E, Traubucchi M (eds) Regulatory peptides: from molecular biology to function. Raven Press, New York, pp 463–470
Zarbin MA, Palacios JM, Wamsley JK, Kuhar MJ (1983) Axonal transport of beta-adrenergic receptors: antero and retrogradely transported receptors differ in agonist affinity and nucleotide sensitivity. Mol Pharmacol 24:341–348
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Zarbin, M.A., Wamsley, J.K. & Kuhar, M.J. Anterograde transport of opioid receptors in rat vagus nerves and dorsal roots of spinal nerves: pharmacology and sensitivity to sodium and guanine nucleotides. Exp Brain Res 81, 267–278 (1990). https://doi.org/10.1007/BF00228115
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DOI: https://doi.org/10.1007/BF00228115