Different Presynaptic Receptors Modulate Neuronal Uptake and Transmitter Release in Serotoninergic Nerve Terminals

  • Salomon Z. Langer
  • Anne-Marie Galzin
Part of the Wenner-Gren Center International Symposium Series book series (WGCISS)


The concept of presynaptic receptors modulating the release of neurotransmitters has arisen from studies on peripheral noradrenergic neurons (Langer, 1974, 1981, Starke, 1981), and has now been extended to the central nervous system for several neurotransmitters, such as noradrenaline, serotonin, acetylcholine and dopamine. It is possible to differentiate between presynaptic inhibitory autoreceptors, acted upon by transmitters which can regulate their own release and in some cases their synthesis, and presynaptic heteroreceptors sensitive to endogenous compounds other than the neuron’s own transmitter. Such substances include co-transmitter neuropeptides, transmitters released from adjacent terminals, or locally or blood-borne substances which can facilitate or inhibit the calcium-dependent release of the neurotransmitter.


Pineal Gland Presynaptic Receptor Neuronal Uptake Lysergic Acid Diethylamide Presynaptic Autoreceptors 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. Airaksinen, M.M. and Kari, I. (1981). B-Carbolines, psychoactive compounds in the mammalian body. Med. Biol., 59, 190–211.Google Scholar
  2. Barbaccia, M.L. and Costa, E. (1984). Autocoids for drug receptors a new approach in drug development. New York Acad. Sci., 430, 103–114.CrossRefGoogle Scholar
  3. Barbaccia, M.L., Gandolfi, O., Chuang, D.M. and Costa, E. (1983). Modulation of neuronal 5HT uptake by a putative endogenous ligand of imipramine recognition sites. Proc. Natl. Acad. Sci. USA, 80, 5134–5138.CrossRefGoogle Scholar
  4. Baumann, P.A. and Waldmeier, P.C. (1981). Further evidence for negative feed-back control of serotonin release in the central nervous system. Naunyn-Schmiedeberg’s Arch. Pharmacol., 317, 3643.Google Scholar
  5. Bradley, P.B., Engel, G., Feniuk, W., Fozard, J.R., Humphrey, P.P.A., Middlemiss, D.N., Mylecharane, E.J., Richardson, B.P. and Saxena, P.R. (1986). Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology, 25, 563–576.CrossRefGoogle Scholar
  6. Cerrito, F. and Raiteri, M. (1979). Serotonin release is modulated by presynaptic autoreceptors. Eur. J. Pharmacol., 57, 427–430.CrossRefGoogle Scholar
  7. Chaput, Y., de Montigny, C. and Blier, P. (1986). Effects of a selective 5HT reuptake blocker, citalopram, on the sensitivity of 5HT autoreceptors: electrophysiological studies in the rat brain. Naunyn-Schmiedeberg’s Arch. Pharmacol., 333, 342–348.CrossRefGoogle Scholar
  8. Engel, G., Göthert, M., Moyer, D., Schlicker, E. and Hillenbrand, K. (1986). Identity of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat brain cortex with 5HT1B binding sites. Naunyn-Schmiedeberg’s Arch. Pharmacol., 332, 1–7.Google Scholar
  9. Farnebo, L.O. and Hamberger, B. (1974). Regulation of [3H]5-hydrox ytr yptamine release from rat brain slices. J. Pharm. Pharmacol., 26, 642–644.CrossRefGoogle Scholar
  10. Galzin, A.M. and Langer, S.Z. (1986). Potentiation by deprenyl of the autoreceptor-mediated inhibition of [H]-5-hydroxytryptamine release by 5-methoxytryptamine. Naunyn-Schmiedeberg’s Arch. Pharmacol., 333, 330–333.Google Scholar
  11. Galzin, A.M., Eon, M.T., Esnaud, H., Lee, C.R., Pévet, P. and Langer, S.Z. Day-night rhythm of 5-methox ytryptamine levels in the pineal gland of the Golden Hamster (Mesocricetus auratus). Endocrinology, submitted.Google Scholar
  12. Galzin, A.M., Moret, C., Verzier, B. and Langer, S.Z. (1985). Interaction between tricyclic and nontricyclic 5-hydroxytryptamine uptake inhibitors and the presynaptic 5-hydroxytryptamine inhibitory autoreceptors in the rat hypothalamus. J. Pharmacol. Exp. Ther., 235, 200–211.Google Scholar
  13. Göthert, M. (1982). Modulation of serotonin release in the brain via presynaptic receptors. Trends in Pharmacol. Sci., 3, 437–440.CrossRefGoogle Scholar
  14. Göthert, M. and Weinheimer, G. (1979). Extracellular 5-hydroxytryptamine inhibits 5-hydrox ytryptamine release from rat brain cortex slices. Naunyn-Schmiedeberg’s Arch. Pharmacol., 310, 93–96.Google Scholar
  15. Habert, E., Graham, D., Tahraoui, L., Claustre, Y. and Langer, S.Z. (1985). Characterization of [3H]-paroxetine binding to rat cortical membranes. Eur. J. Pharmacol., 118, 107–114.CrossRefGoogle Scholar
  16. Hamon, M., Bourgoin, S., Jagger, J. and Glowinski, J. (1974). Effects of LSD on synthesis and release of 5-HT in rat brain slices. Brain Res., 69, 265–280.CrossRefGoogle Scholar
  17. Kamal, L., Arbilla, S., Galzin, A.-M. and Langer, S.Z. (1983). Agiphetamine inhibits the electrically evoked release of [33H]dopamine from slices of the rabbit caudate. J. Pharmacol. Exp. Ther., 227, 446–458.Google Scholar
  18. Kari, I. (1981). 6-Methoxy-1,2,3,4-tetrahydro-B-carboline in pineal gland of chicken and cock. FEBS Lett., 127, 277–280.CrossRefGoogle Scholar
  19. Kari, I., Airaksinen, M.M., Gynther, J. and Huhtikangas, A. (1983). Mass spectrometric identification of 6-methoxy-1,2,3,4-tetrahydro-B-carboline in pineal gland. In Recent developments in biochemistry, medicine and environmental research. (ed. A. Frigerio). 8, Elsevier, Amsterdam.Google Scholar
  20. Langer, S.Z. (1974). Presynaptic regulation of catecholamine release. Biochem. Pharmacol. 23, 1793–1800.CrossRefGoogle Scholar
  21. Langer, S.Z. (1981). Presynaptic regulation of the release of catecholamines. Pharmacol. Rev., 32, 337–362.Google Scholar
  22. Langer, S.Z. (1984). [3H]imipramine and [3H]desipramine binding non-specific displaceable sites or physiologically relevant sites associated with the uptake of serotonin and noradrenaine? Trends in Pharmacol. Sci., 5, 51–52.CrossRefGoogle Scholar
  23. Langer, S.Z. and Moret, C. (1982). Citalopram antagonizes the stimulation by lysergic acid diethylamide of presynaptic inhibitory serotonin autoreceptors in the rat hypothalamus. J. Pharmacol. Exp. Ther., 222, 220–226.Google Scholar
  24. Langer, S.Z. and Raisman, R. (1983). Binding of [3H]imipramine and [H]desipramine as biochemical tools for studies in depression. Neuropharmacology, 22, 407–413.CrossRefGoogle Scholar
  25. Langer, S.Z., Briley, M.S., Raisman, R., Henry, J.F. and Morselli, P.L. (1980a). Specific 3H-imipramine binding in human platelets: influence of age and sex. Naunyn-Schmiedeberg’s Arch. Pharmacol., 313, 189–194.Google Scholar
  26. Langer, S.Z., Lee, C.R., Schoemaker, H., Segonzac, A. and Esnaud, H. (1985). 5-Methoxytryptoline and close analogs as candidates for the endogenous ligand of the 3H-imipramine recognition site. In Endocoids. (eds. H. Lal, F. Labella and J. Lane). Alan R. Liss, New York, pp. 441–455.Google Scholar
  27. Langer, S.Z., Lee, C.R., Segonzac, A., Tateishi, T., Esnaud, H., Schoemaker, H. and Winblad, B. (1984b). Possible endocrine role of the pineal gland for 6-methoxytetrahydro-beta-carboline, a putative endogenous neuromodulator of the [H]imipramine recognition site. Eur. J. Pharmacol., 102, 379–380.CrossRefGoogle Scholar
  28. Langer, S.Z., Moret, C., Raisman, R., Dubocovich, M.L. and Briley, M.S. (1980b). High-affinity [3H]imipramine binding in rat hypothalamus is associated with the uptake of serotonin but not norepinephrine. Science, 210, 1133–1135.CrossRefGoogle Scholar
  29. Unger, S.Z., Raisman, R. and Briley, M.S. (1981a). High-affinity [H]DMI binding is associated with neuronal noradrenaline uptake in the periphery and the central nervous system. Eur. J. Pharmacol., 72, 423–424.CrossRefGoogle Scholar
  30. Langer, S.Z., Raisman, R., Tahraoui, L., Scatton, B., Niddam, R., Lee, C.R. and Claustre, Y. (1984a). Substituted tetrahydro-B- c~rbolines are possible candidates as endogenous ligand of the [H]imipramine recognition site. Eur. J. Pharmacol., 98, 153–154.CrossRefGoogle Scholar
  31. Langer, S.Z., Galzin, A.M., Lee, C.R. and Schoemaker, H. (1986) Antidepressant binding sites in brain and platelets In Antidepressants and receptor function Ciba Foundation Symposium 123, John Wiley and Sons, pp. 3–29.Google Scholar
  32. Langer, S.Z., Zarifian, E., Briley, M.S., Raisman, R. and Sechter, D. (1981b). High-affinity binding of 3H-imipramine in brain and platelets and its relevance to the biochemistry of affective disorders. Life Sci., 29, 211–218.CrossRefGoogle Scholar
  33. Leino, M., Kari, I., Airaksinen, M.M. and Gynther, J. (1983). 6-Methoxy-tetrahydro-B-carboline in the retinae of rabbits and pigs. Exp. Eye Res., 36, 135–138.CrossRefGoogle Scholar
  34. Lewis, D.A. and McChesney, C. (1985). Tritiated imipramine binding distinguishes among subtypes of depression. Arch. Gen. Psychiatry, 42, 485–488.CrossRefGoogle Scholar
  35. Maura, G. and Raiteri, M. (1984). Functional evidence that chronic drugs induce adaptive changes of central autoreceptors regulating serotonin release. Eur. J. Pharmacol., 97, 309–313.CrossRefGoogle Scholar
  36. Paul, S.M., Rehavi, M., Skolnick, P., Ballenger, J.C. and Goodwin, F.K. (1981). Depressed patients have decreased binding of tritiated imipramine to the platelets serotonin “transporter”. Arch. Gen. Psychiatry, 38, 1315–1317.CrossRefGoogle Scholar
  37. Passarelli, F., Galzin, A.M. and Langer, S.Z. Interaction between neuronal uptake inhibitors and presynaptic serotonin autoreceptors in rat hypothalamic slices: comparison of K+ and electrical depolarization. J. Pharmacol. Exp. Ther., submitted.Google Scholar
  38. Pelayo, F., Dubocovich, M.L. and Langer, S.Z. (1980). Inhibition of neuronal uptake reduces the presynaptic effects of clonidine but nqt of a-methylnoradrenaline on the stimulation-evoked release of [H]-noradrenaline from rat occipital cortex slices. Eur. J. Pharmacol., 64, 143–155.CrossRefGoogle Scholar
  39. Pettibone, D.J. and Pflueger, A.B. (1984). Effects of methiothepin and lysergic acid diethylamide on serotonin release in vitro and serotonin synthesis in vivo. possible relation to serotonin autoreceptor function. J. Neurochem., 43, 83–90.CrossRefGoogle Scholar
  40. Pévet, P. (1983). Is 5-methoxytryptamine a pineal hormone? Psychoneuroendocrinology, 8, 61–73.CrossRefGoogle Scholar
  41. Poirier, M.F., Benkelfat, C., Loo, H., Sechter, D., Zarifian, E., Galzin, A.M. and Langer, S.Z. (1986). Reduced BB, of [3H]-imipramine binding to platelets of depressed patientg-free of previous medication with 5HT uptake inhibitors. Psychopharmacol., 89, 456–461.CrossRefGoogle Scholar
  42. Raisman, R., Briley, M.S., Bouchami, F., Sechter, D., Zarifian, E. and Langer, S.Z. (1982b). 3H-Imipramine binding and serotonin uptake in platelets from untreated depressed patients and control volunteers. Psychopharmacol., 77, 332–335.CrossRefGoogle Scholar
  43. Raisman, R., Sette, M., Pimoule, C., Briley, M.S. and Langer, S.Z. (1982a). High affinity [3H]desipramine binding in the peripheral and central nervous system: a specific site associated with the neuronal uptake of noradrenaline. Eur. J. Pharmacol., 78, 345–351.CrossRefGoogle Scholar
  44. Schlicker, E., Brandt, F., Classen, K. and Gthert, M. (1985). Serotonin release in human cerebral cortex and its modulation via serotonin receptors. Brain Res., 331, 337–341.CrossRefGoogle Scholar
  45. Schoemaker, H., Pimoule, C., Arbilla, S., Scatton B., Javoy-Agid, F. and Langer S.Z. (1985). Sodium-dependent [H]cocaine binding associated with dopamine uptake sites in the rat striatum and human putamen decrease after dopaminergic denervation and in Parkinson’s disease. Naunyn-Schmiedeberg’s Arch. Pharmacol., 329, 227–235.Google Scholar
  46. Segonzac, A., Schoemaker, H., Tateishi, T. and Langer, S.Z. (1985). 5-Methoxytryptoline, a competitive endocoid acting at 3H-imipramine recognition sites in human platelets. J. Neurochem., 45, 249–256.CrossRefGoogle Scholar
  47. Verg€, D., Daval, G., Patey, A., Gozlan, H., El-Mestikawy, S. and Hamon, M. (1985). Presynaptic 5-HT autoreceptors on serotonergic cell bodies and/or dendrites but not terminals are of the 5HTIA subtype. Eur. J. Pharmacol., 113, 463–464.CrossRefGoogle Scholar

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© The Wenner-Gren Center 1987

Authors and Affiliations

  • Salomon Z. Langer
  • Anne-Marie Galzin

There are no affiliations available

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