Summary
The effects of various cholinergic agonists and antagonists on the spontaneous release of newly synthetized 3H-5-HT were examined in rat hypothalamic slices. 3H-5-HT was measured in incubating medium at the end of a 30 min incubation carried out with l-3H-tryptophan in the presence of the various durgs tested. ACh (10−5 M) in the presence of eserine (2×10−4 M), and carbachol (10−5 M) stimulated the release of 3H-5-HT. In contrast, oxotremorine (10−5 M) reduced the 3H-amine release. The effect of carbachol was blocked by two nicotinic blockers, mecamylamine (10−6 M) and d-tubocurarine (10−6 M). It was not reduced by the muscarinic antagonists, atropine (10−6 M) and scopolamine (10−6 M). In fact, each of two antagonists added alone to the incubating medium enhanced 3H-5-HT release. The scopolamine (10−6 M) stimulating effect on 3H-5-HT release was suppressed by d-tubocurarine (10−6 M). Finally, the inhibiting effect of oxotremorine on 3H-5-HT release was not prevented by d-tubocurarine (10−6 M) but was in the presence of atropine (10−6 M) or scopolamine (10−6 M).
In the concentrations used in the release study, the cholinergic agonists and antagonists had no effect on the total formation of 3H-5-HT and 3H-5-HIAA from l-3H-tryptophan and on the accumulation of l-3H-tryptophan in tissues. In these concentrations, except for eserine, they did not affect the uptake of exogenous 3H-5-HT in hypothalamic synaptosomes (P2 fraction).
These results suggest that cholinergic receptors of the muscarinic and nicotinic type are involved in the control of 3H-5-HT release; since the stimulation of the muscarinic and nicotonic cholinergic receptors resulted in an inhibition and an activation of 3H-5-HT release, respectively. As in the case of peripheral noradrenergic and central dopaminergic neurons the cholinergic receptors could be localized on serotoninergic terminals.
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References
Balfour, D. J. K.: Effects of nicotine on the uptake and retention of 14C-noradrenaline and 14C-5-hydroxytryptamine by rat brain homogenates. Europ. J. Pharmacol. 23, 19–26 (1973)
Besson, M. J.: Mécanismes de Régulation de la Biosynthèse et de la Libération de la Dopamine au Niveau des Terminaisons Dopaminergiques du Système Nigro-Striatal chez le Rat et le Chat. Thèse de Doctorat d'Etat es Sciences Naturelles. Paris 1973
Burn, J. H., Rand, M. J.: A new interpretation of the adrenergic nerve fibre. Advanc. Pharmacol. 1, 1–30 (1962)
Feigenson, M. E., Saelens, J. K.: An enzyme assay for acetylcholine. Biochem. Pharmacol 18, 1479–1486 (1969)
Fiorindo, R., Justo, G., Motta, M., Simonovic, I., Martini, L.: Acetylcholine and the secretion of pituitary gonadotropins. In: “Hypothalamic Hormones” (M. Motta, P. G. Crosignani and L. Martini, eds.), pp. 195–204 New York-London: Academic Press, 1975
Fuxe, K.: Evidence for the existence of monoamine neurons in the central nervous system. IV. Distribution of monoamine terminals in the central nervous system. Acta physiol. scand. 64, Suppl. 247, 36–85 (1965)
Giorguieff, M. F., Le Floc'h, M. L., Glowinski, J., Besson, M. J.: Involvement of cholinergic presynaptic receptors of nicotinic and muscarinic types in the control of the spontaneous release of dopamine from striatal dopaminergic terminals in the rat. J. Pharmacol. exp. Ther. (in press, 1976b)
Giorguieff, M. F., Le Floc'h, M. L., Westfall, T. C., Glowinski, J., Besson, M. J.: Nicotinic effect of acetylcholine on the release of newly synthetized 3H-dopamine in rat striatal slices and cat caudate nucleus. Brain Res. 106, 117–131 (1976a)
Goodman, F. R., Weiss, G. B.: Alteration of 5-hydroxytryptamine-14C efflux by nicotine in rat brain area slices. Neuropharmacology 12, 955–965 (1973)
Gray, E. G., Whittaker, V. P.: The isolation of nerve endings from brain: an electron microscopic study of cell fragments derived by homogenization and centrifugation. J. Anat. (Lond.) 96, 79–88 (1962)
Haeusler, G., Thoenen, H., Haefely, W., Hurlimann, A.: Electrical events in cardiac adrenergic nerves and noradrenaline release from the heart induced by acetylcholine and KCl. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 261, 389–411 (1968)
Hamon, M., Bourgoin, S., Héry, F., Glowinski, J.: In vitro Ca2+ dependent proteolysis in brain tissues: A possible source of error in transmitter metabolism studies. J. Neurochem. 23, 849–856 (1974a)
Hamon, M., Bourgoin, S., Jagger, J., Glowinski, J.: Effect of LSD on synthesis and release of 5-HT in rat brain slices. Brain Res. 69, 265–280 (1974b)
Héry, F., Rouer, E., Glowinski, J.: Daily variations of serotonin metabolism in the rat brain. Brain Res. 43, 445–465 (1972)
Hoffmann, F., Hoffmann, E. J., Middleton, S., Talesnik, J.: The stimulating effect of acetylcholine on the mammalian heart and the liberation of an epinephrine-like substance by the isolated heart. Amer. J. Physiol. 144, 189–198 (1945)
Jones, B. E., Guyenet, P., Chéramy, A., Gauchy, C., Glowinski, J.: The in vivo release of acetylcholine from cat caudate nucleus after pharmacological and surgical manipulation of dopaminergic nigrostriatal neurons. Brain Res. 64, 355–369 (1973)
Koelle, G. B.: Parasympathomimetic agents. In: “The pharmacological basis of therapeutics” third edition (Goodman and Gilman, eds.), pp. 464–476. New York: MacMillan Comp. 1965
Lindmar, R., Löffelholz, K., Muscholl, E.: A muscarinic mechanism inhibiting the release of noradrenaline from peripheral adrenergic nerve fibres by nicotine agents. Brit. J. Pharmacol. Chemother. 32, 280–294 (1968)
Lowry, O. H., Rosebrough, N. J., Farr, A. L., Randall, R. J.: Protein measurement with the folin phenol reagent. J. biol. Chem. 193, 265–275 (1951)
Miyamoto, M. D., Volle, R. L.: Enhancement by carbachol of transmitter release from nerve terminals. Proc. nat. Acad. Sci. (Wash.) 71, 1489–1492 (1974)
Muscholl, E.: Cholinomimetic drugs and release of the adrenergic transmitter. In: New aspects of storage and release mechanisms of catecholamines (Schumann and Kroneberg, eds.), pp. 168–186. Berlin-Heidelberg-New York: Springer 1970
Muscholl, E.: Muscarinic inhibition of the norepinephrine release from peripheral sympathetic fibres. In: Pharmacology and the future of man: brain, nerves and synapses (G. H. Acheson, main editor), vol. 4, pp. 440–457 (1973)
Myers, R. D.: Chemical mechanisms in the hypothalamus mediating eating and drinking in the monkey. Ann. N. Y. Acad. Sci. 157, 918–933 (1969)
Myers, R. D.: The role of hypothalamic transmitter factors in the control of body temperature. In: Physiological and behavioural temperature regulation (J. D. Hardy et al., eds.), pp. 648–666. Springfield, Ill.: Ch. C. Thomas 1970
Polak, R. L.: Stimulating action of atropine on the release of acetylcholine by rat cerebral cortex in vitro. Brit. J. Pharmacol. 41, 600–606 (1971)
Polz-Tejera, G., Schmidt, J., Karten, H. J.: Autoradiographic localisation of α-bungarotoxin-binding sites in the central nervous system. Nature (Lond.) 258, 349–351 (1975)
Saavedra, J. M., Palkovits, M., Brownstein, M. J., Axelrod, J.: Serotonin distribution in the nuclei of the rat hypothalamus and preoptic region. Brain Res. 77, 157–165 (1974)
Sethy, V. H., Roth, R. H., Kuhar, M. J., Van Woert, M. H.: Choline and acetylcholine: Regional distribution and effect of degeneration of cholinergic nerve terminals in the rat hippocampus. Neuropharmacology 12, 819–823 (1973)
Snedecor, G. W., Cochran, W. G.: Statistical methods. Ames: Iowa State University Press 1967
Snyder, S. H.: Putative neurotransmitters in the brain: Selective neuronal uptake, subcellular localization and interactions with centrally acting drugs. Biol. Psychiat. 2, 367–389 (1970)
Terpstra, G. K., and Slangen, J. L.: Central blockade of (methyl) atropine on carbachol drinking: A dose response study. Physiol. Behav. 8, 715–719 (1972)
Westfall, T. C.: Effect of nicotine and other drugs on the release of 3H-norepinephrine and 3H-dopamine from rat brain slices. Neuropharmacology 13, 693–700 (1974)
Yaksh, T. L., Yamamura, H. I.: The release in vivo of 3H-acetylcholine from cat caudate nucleus and cerebral cortex by atropine, pentylenetetrazol, K+-depolarization and electrical stimulation. J. Neurochem. 25, 123–130 (1975)
Yamamura, H. I., Kuhar, M. J., Snyder, S. H.: In vivo identification of muscarinic cholinergic receptor binding in rat brain. Brain Res. 80, 170–176 (1974)
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Héry, F., Bourgoin, S., Hamon, M. et al. Control of the release of newly synthetized 3H-5-hydroxytryptamine by nicotinic and muscarinic receptors in rat hypothalamic slices. Naunyn-Schmiedeberg's Arch. Pharmacol. 296, 91–97 (1977). https://doi.org/10.1007/BF00508459
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DOI: https://doi.org/10.1007/BF00508459