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The role of various calcium and potassium channels in the regulation of somatodendritic serotonin release

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Abstract

We prepared slices from midbrain containing the raphe nuclei and from hippocampus of rats. The brain slices were loaded with [3H]serotonin and superfused in order to measure the release of radioactivity at rest and in response to electrical stimulation. No difference was observed in the resting and stimulated fractional release of tritium in the somatodendritic and axon terminal parts of serotonergic neurons. The selective 5-HT1A receptor agonist 8-OH-DPAT decreased the electrically induced tritium effux from raphe nuclei slices preloaded with [3H]serotonin, and this inhibition was reversed by 5-HT1A receptor antagonist (+)WAY-100135. The 5-HT1B receptor agonist CGS-12066B but not 8-OH-DPAT, inhibited the stimulation-evoked tritium efflux from hippocampal slices after labeling with [3H]serotonin. The electrical stimulation-evoked tritium efflux in raphe nuclei slices incubate with [3H]serotonin was completely external Ca2+-dependent, and omega-conotoxin GVIA and Cd2+, but not diltiazem, inhibited the tritium overflow. In raphe nuclei slices 4-aminopyridine enhanced the electrical stimulation-induced trititum release in a concentration-dependent manner. The inhibition of tritium efflux by 8-OH-DPAT was abolished with 4-aminopyridine. Glibenclamide or tolbutamide proved to be ineffective. These data indicate that (1) different 5-HT receptor subtypes (5-HT1A and 5-HT1B) regulate dendritic and axon terminal 5-HT release; (2) serotonin release from the dendrites may be regulated by the voltage-sensitive N-type Ca2+ channels; (3) the 5-HT1A receptor-mediated inhibition of serotonin release may be due to opening of voltage-sensitive K+ channels.

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References

  1. Blier, P., Lista, A., and De Montigny, C. 1993. Differential properties of pre- and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus: II. Effect of pertussis and cholera toxins. J. Pharm. Exp. Ther. 265:16–23.

    Google Scholar 

  2. Palacios, J. M., Pazos, A., and Hoyer, D. 1987. Characterization and mapping of 5-HT1A sites in the brain of animals and man. Pages: 67–81,in Dourish, C. T., Ahlenins, S., Hutson, P. H. (eds.) Brain 5-HT1A Receptors Ellis Horwood, Chichester.

    Google Scholar 

  3. Engel, G., Gothert, M., Hoyer, D., Schlicker, E., and Hillenbrand, K. 1986. Identify of inhibitory presynaptic 5-hydroxytryptamine (5-HT) autoreceptors in the rat cortex with 5-HT1B binding sites. Naunyn-Schmiedeberg's Arch. Pharmacol. 332:1–7.

    Google Scholar 

  4. Innis, R. B., Nestler, E. J., and Aghajanian, G. K. 1988. Evidence for G protein mediation of serotonin and GABAB-induced hyperpolarization in rat dorsal raphe neurons. Brain Res. 459:27–36.

    Google Scholar 

  5. Blier, P. 1991. Terminal serotonin autoreceptor function in the rat hippocampus is not modified by pertussis and cholera toxins. Naunyn-Schmiedeberg's Arch. Pharmacol. 344:160–166.

    Google Scholar 

  6. Lipscombe, D., Kongsamut, S., and Tsien, R. W. 1989. Alphaadrenergic inhibition of sympathetic neurotransmitter release mediated by modulation of N-type calcium-channel gating. Nature 340:639–632.

    Google Scholar 

  7. Diverse-Pierluissi, M., Goldsmith, P. K., and Dunlap, K. 1995. Transmitter-mediated inhibition of N-type calcium channels in sensory neurons involves multiple GTP-binding proteins and subunit. Neuron 14:191–200.

    Google Scholar 

  8. Hu, P.-S., and Fredholm, B. B. 1989. Alpha2-adrenoceptor agonist-mediated inhibition of [3H]noradrenaline release from rat hippocampus is reduced by 4-aminopyridine, but that caused by an adenosine analogue or omega-conotoxin is not. Acta Physiol. Scand. 136:347–353.

    Google Scholar 

  9. Torocsik, A., and Vizi, E. S. 1990. 4-Aminopyridine interrupts the modulation of acetylcholine release mediated by muscarinic and opiate receptors. J. Neurosci. Res. 27:228–232.

    Google Scholar 

  10. Allgaier, C., Feuerstein, T. J., and Hertting, G. 1986. N-ethylmaleimide (NEM) diminishes alpha2-adrenoceptor mediated effects on noradrenaline release. Naunyn-Schmiedeberg's Arch. Pharmacol. 331:239.

    Google Scholar 

  11. Bowyer, J. F., and Weiner, N. 1988. K+ channel and adenylate cyclase involvement in regulation of Ca2+-evoked release of [3H]dopamine from synaptosomes. J. Pharmacol. Exp. Ther. 248:514–520.

    Google Scholar 

  12. Kerwin, R. W., and Pycock, C. J. 1979. The effect of some putative neurotransmitters on the release of 5-hydroxytryptamine and gamma-aminobutyric acid from slices of the rat midbrain raphe area.Neuroscience 4:1359–1365.

    Google Scholar 

  13. Glowinski, J., and Iversen, L. L. 1966. Regional studies of catecholamines in the rat brain. The disposition of (3H)norepinephrine, (3H)dopamine and (3H)DOPA in various regions of the brain. J. Neurochem. 13:655–699.

    Google Scholar 

  14. Harsing, L. G., Jr., Sershen, H., and Lajtha, A. 1992. Dopamine efflux from striatum after chronic nicotine: evidence for autore ceptor desensitization. J. Neurochem. 59:48–54.

    Google Scholar 

  15. Schlicker, E., Gothert, M., and Clausing, R. 1982. Acute and chronic changes of noradrenergic transmission do not affect the alpha-adrenoceptor-mediated inhibition of [3H]serotomin release in the cerebral cortex. Naunyn-Schmiedeberg's Arch. Pharmacol. 320:38–44.

    Google Scholar 

  16. Dahlstrom, A., and Fuxe, K. 1964. Evidence for the existence of monoamine containing neurons in the central nervous system 1. Demonstration of monoamines in the cell bodies of brain stem neurons. Acta Physiol. Scand. Suppl. 232:1–55.

    Google Scholar 

  17. Bagdy, E., Horvath, E., Sziraki, I., Kiraly, I., Harsing, L. G. 1994. Further evidence on 5-HT1A agonist action of 8-OH-DPAT, in vitro release studies. 17th Annual Meeting of the European Neuroscience Association Abstract 51.19.

  18. Zifa, E., and Fillion, G. 1992. 5-Hydroxytryptamine receptors. Pharmacol. Rev. 44:401–458.

    Google Scholar 

  19. Verge, 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 5-HT1A subtype. Eur. J. Pharmacol. 113:463–464.

    Google Scholar 

  20. Cliffe, I. A., Brightwell, C. I., Fletcher, A., Forster, E. A., Mansell, H. L., Reilly, Y., Routledge, C., and White, A. C. 1993. (S)-Ntert-Butyl-3-(4-(2-methoxyphenyl)-piperazin-1-yl)-2-phenylpropanamide [(S)-WAY-100135]: a selective antagonist at presynaptic and postsynaptic 5-HT1A receptors. J. Med. Chem. 36:1509–1510.

    Google Scholar 

  21. Neale, R. F. Fallon, S. L., Royar, W. C., Wasley, J. W. F., Martin, L. L., Stone, G. A., Glaester, B. S., Sinton, C. M., and Williams, M. 1987. Biochemical and pharmacological characterization of CGS 12066B, a selective 5-HT1B agonist. Eur. J. Pharmacol. 136:1–9.

    Google Scholar 

  22. Middlemiss, D. N. 1984. Stereoselective blockade at [3H]5-HT binding sites and at the 5-HT autoreceptor by (−)propranolol. Eur. J. Pharmacol. 101:289–293.

    Google Scholar 

  23. Schoeffter, P., and Hoyer, D. 1989. 5-Hydroxytryptamine 5-HT1B and 5-HT1D receptors mediating inhibition of adenylate cyclase activity. Pharmacological comparison with special reference to the effects of yohimbine, rauwolscine and some beta-adrenoceptor antagonists. Naynyn-Schmiedbergs,'s Arch. Pharmacol. 340:285–292.

    Google Scholar 

  24. Innis, R. B., and Aghajanian, G. K. 1987. Pertussis toxin blocks 5-HT1A and GABAB receptor mediated inhibition of serotonergic neurons. Eur. J. Pharmacol. 143:195–204.

    Google Scholar 

  25. Andrade, R., Malenka, R. C., and Nicoll, R. A. 1986. A G protein couples serotonin and GABAB receptors to the same channels in hippocampus. Science 234:1261–1265.

    Google Scholar 

  26. Rudy, B. 1988. Diversity and ubiquity of K channels. Neuroscience 25:729–749.

    Google Scholar 

  27. Illes, P. 1986. Mechanisms of receptor-mediated modulation of transmitter release in noradrenergic, cholinergic and sensory neurons. Neuroscience 14:909–928.

    Google Scholar 

  28. Haj-Dahmane, S., Hamon, M., and Lanfumey, L. 1991. K+ channel and 5-hydroxytryptamine 1A autoreceptor interactions in the rat dorsal raphe nucleus: an in vitro electrophysiological study. Neuroscience 41:495–505.

    Google Scholar 

  29. Cook, N. S. 1988. The pharmacology of potassium channels and their therapeutic potential. Trends Pharmacol. Sci. 9:21–28.

    Google Scholar 

  30. de Erausquin, G., Brooker, G., and Hanbauer, I. 1992. K+-evoked dopamine release depends on a cytosolic Ca2+ pool regulated by N-type Ca2+ channels. Neurosci. Lett. 145:1211–1215.

    Google Scholar 

  31. Herdon, H., and Nahorski, S. R. 1989. Investigation of the roles of dihydropyridine and ω-conotoxin-sensitive calcium channels in mediating depolarisation-evoked endogenous dopamine release from striatal slices. Naunyn-Schmiedeberg's Arch. Pharmacol. 340:36–40.

    Google Scholar 

  32. Zimanyi, I., Somogyi, G. T., Harsing, L. G. Jr., Vizi, E. S. 1985. Release of3H-noradrenaline by 4-aminopyridine and alpha-2 adrenoceptor agonists. Pages:333–334,in Szabadi, E., Bradshaw, 3C. M., Nahorski, S. R. (eds.) Pharmacology of Adrenoceptors Mac-Millan Press Ltd. London.

    Google Scholar 

  33. Harsing, L. G., Jr., Sershen, H., Vizi, E. S., and Lajtha, A. 1992. N-type calcium channels are involved in the dopamine releasing effect of nicotine. Neurochem. Res. 17:729–734.

    Google Scholar 

  34. Gauer, S., Newcomb, R., Rivnay, B., Bell, J. R., Yamashiro, D., Ramachandran, J., and Miljanich, G. P. 1994. Calcium channel antagonist peptides define several components of transmitter release in the hippocampus. Neuropharmacology 33:1211–1219.

    Google Scholar 

  35. Dunlap, K., Luebke, J. I., and Turner, T. J. 1995. Exocytotic Ca2+ channels in mammalian central neurons. Trends Neurosci. 18:89–98.

    Google Scholar 

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  1. Institute for Drug Research, 47-49 Berlini u., H-1450, Budapest, Hungary

    Erzsebet Bagdy &  Laszlo G. Harsing Jr.

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  2. Laszlo G. Harsing Jr.
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Bagdy, E., Harsing, L.G. The role of various calcium and potassium channels in the regulation of somatodendritic serotonin release. Neurochem Res 20, 1409–1415 (1995). https://doi.org/10.1007/BF00970588

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