Summary
Slices of the rabbit occipito-parietal cortex were preincubated with 3H-serotonin and then superfused and stimulated electrically (2 min at 3 Hz). In the absence of drugs, the stimulation-evoked overflow of tritium was approximately 3% of the tritium content of the tissue. Unlabelled serotonin and 5-carboxamido-tryptamine, when administered in the presence of 6-nitroquipazine, reduced the evoked overflow of tritium. Their effects were antagonized by metitepin (apparent pA2 value 8.1) and (±)-cyanopindolol (apparent pA2 value 6.4). Metitepin, but not cyanopindolol, increased evoked tritium overflow; the effect of metitepin was greater in the presence than in the absence of nitroquipazine. The evoked overflow of tritium was also depressed by clonidine, an effect antagonized by idazoxan (apparent pA2 value 7.0) but not by prazosin. Phenylephrine caused a decrease only at high concentrations that simultaneously accelerated basal tritium efflux. Prazosin and idazoxan did not change evoked tritium overflow, and phentolamine increased it significantly only when administered in the presence of (+)-oxaprotiline. Rauwolscine produced an inhibition that was prevented by metitepin. It is concluded that the serotonergic axons of the rabbit occipitoparietal cortex possess presynaptic, release-inhibiting serotonin autoreceptors and α2-adrenoceptors. The receptors appear to receive an input of endogenous serotonin and, to a lesser extent, noradrenaline, under the conditions of these in vitro experiments.
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References
Baumann PA, Waldmeier PC (1981) Further evidence for negative feedback control of serotonin release in the central nervous system. Naunyn-Schmiedeberg's Arch Pharmacol 317:36–43
Beavan MA (1975) Radiochemical assay procedures for drugs and transmitters. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 1. Plenum Press, New York, pp 253–290
Cerrito F, Raiteri M (1979) Serotonin release is modulated by presynaptic autoreceptors. Eur J Pharmacol 57:427–430
Classen K, Göthert M, Schlicker E (1984) Effects of DU 24565 (6-nitroquipazine) on serotoninergic and noradrenergic neurones of the rat brain and comparison with the effects of quipazine. Naunyn-Schmiedeberg's Arch Pharmacol 326:198–202
Engel G, Göthert M, Müller-Schweinitzer E, Schlicker E, Sistonen L, Stadler PA (1983) Evidence for common pharmacological properties of [3H]5-hydroxytryptamine binding sites, presynaptic 5-hydroxytryptamine autoreceptors in CNS and inhibitory presynaptic 5-hydroxytryptamine receptors on sympathetic nerves. Naunyn-Schmiedeberg's Arch Pharmacol 324:116–124
Ennis C (1983) The release of 5-hydroxytryptamine in the occipital and frontal cortex is modulated by different subtypes of α-adrenoceptor. J Pharm Pharmacol 35:750–751
Farnebo LO, Hamberger B (1973) Catecholamine release and receptors in brain slices. In: Usdin E, Snyder SH (eds) Frontiers in catecholamine research. Pergamon Press, New York, pp 589–593
Farnebo LO, Hamberger B (1974) Regulation of [3H]5-hydroxytryptamine release from rat brain slices. J Pharm Pharmacol 26:642–644
Feuerstein TJ, Hertting G, Jackisch R (1985a) Modulation of hippocampal serotonin (5-HT) release by endogenous adenosine. Eur J Pharmacol 107:233–242
Feuerstein TJ, Hertting G, Jackisch R (1985b) Endogenous noradrenaline as modulator of hippocampal serotonin (5-HT)-release. Naunyn-Schmiedeberg's Arch Pharmacol 329:216–221
Frankhuyzen AL, Mulder AH (1980) Noradrenaline inhibits depolarization-induced 3H-serotonin release from slices of rat hippocampus. Eur J Pharmacol 63:179–182
Frankhuyzen AL, Mulder AH (1982) Pharmacological characterization of presynaptic α-adrenoceptors modulating [3H]noradrenaline and [3H]5-hydroxytryptamine release from slices of the hippocampus of the rat. Eur J Pharmacol 81:97–106
Furchgott RF (1972) The classification of adrenoceptors (adrenergic receptors). An evaluation from the standpoint of receptor theory. In: Blaschko H, Muscholl E (eds) Catecholamines. Handbook of experimental pharmacology, vol 33. Springer, Berlin Heidelberg New York, pp 283–335
Galzin AM, Moret C, Langer SZ (1984) Evidence that exogenous but not endogenous norepinephrine activates the presynaptic alpha-2 adrenoceptors on serotonergic nerve endings in the rat hypothalamus. J Pharmacol Exp Ther 228:725–732
Göthert M (1980) Serotonin-receptor-mediated modulation of Ca2+-dependent 5-hydroxytryptamine release from neurones of the rat brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 314:223–230
Göthert M (1982) Modulation of serotonin release in the brain via presynaptic receptors. Trends Pharmacol Sci 3:437–440
Göthert M, Huth H (1980) Alpha-adrenoceptor-mediated modulation of 5-hydroxytryptamine release from rat brain cortex slices. Naunyn-Schmiedeberg's Arch Pharmacol 313:21–26
Göthert M, Weinheimer G (1979) Extracellular 5-hydroxytryptamine inhibits 5-hydroxytryptamine release from rat brain cortex slices. Naunyn-Schmiedeberg's Arch Pharmacol 310:93–96
Göthert M, Huth H, Schlicker E (1981) Characterization of the receptor subtype involved in alpha-adrenoceptor-mediated modulation of serotonin release from rat brain cortex slices. Naunyn-Schmiedeberg's Arch Pharmacol 317:199–203
Hamon M, Bourgoin S, Jagger J, Glowinski J (1974) Effects of LSD on synthesis and release of 5-HT in rat brain slices. Brain Res 69:265–280
Heepe P, Starke K (1985) α-Adrenoceptor antagonists and the release of noradrenaline in rabbit cerebral cortex slices: support for the α-autoreceptor hypothesis. Br J Pharmacol 84:147–155
Lane AC, Howlett DR, Walter DS (1983) The effects of metal ions on the binding of a new α2-adrenoceptor antagonist radioligand (3H)-RX 781094 in rat cerebral cortex. Biochem Pharmacol 32:3122–3125
Langer SZ, 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
Martin LL, Sanders-Bush E (1982) Comparison of the pharmacological characteristics of 5 HT1 and 5 HT2 binding sites with those of serotonin autoreceptors which modulate serotonin release. Naunyn-Schmiedeberg's Arch Pharmacol 321:165–170
Maura G, Gemignani A, Raiteri M (1982) Noradrenaline inhibits central serotonin release through alpha2-adrenoceptors located on serotonergic nerve terminals. Naunyn-Schmiedeberg's Arch Pharmacol 320:272–274
Middlemiss DN (1984) Stereoselective blockade at [3H]5-HT binding sites and at the 5-HT autoreceptor by propranolol. Eur J Pharmacol 101:289–293
Monachon MA, Burkard WP, Jalfre M, Haefely W (1972) Blockade of central 5-hydroxytryptamine receptors by methiothepin. Naunyn-Schmiedeberg's Arch Pharmacol 274:192–197
Mounsay I, Brady KA, Carroll J, Fisher R, Middlemiss DN (1982) K+-evoked [3H]5-HT release from rat frontal cortex slices: The effect of 5-HT agonists and antagonists. Biochem Pharmacol 31:49–53
Reichenbacher D, Reimann W, Starke K (1982) α-Adrenoceptor-mediated inhibition of noradrenaline release in rabbit brain cortex slices. Naunyn-Schmiedeberg's Arch Pharmacol 319:71–77
Richards MH (1985) Efflux of 3H-5-hydroxytryptamine from rat hypothalamic slices by continuous electrical stimulation: Frequency-dependent responses to serotonergic antagonists and 5-hydroxytryptamine. Naunyn-Schmiedeberg's Arch Pharmacol 329:359–366
Schlicker E, Brandt F, Classen K, Göthert M (1985a) Serotonin release in human cerebral cortex and its modulation via serotonin receptors. Brain Res 331:337–341
Schlicker E, Göthert M, Hillenbrand K (1985b) Cyanopindolol is a highly potent and selective antagonist at the presynaptic serotonin autoreceptor in the rat brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 331:398–401
Starke K (1981a) Presynaptic receptors. Ann Rev Pharmacol Toxicol 21:7–30
Starke K (1981b) α-Adrenoceptor subclassification. Rev Physiol Biochem Pharmacol 88:199–236
Starke K, Montel H (1973) Involvement of α-receptors in clonidine-induced inhibition of transmitter release from central monoamine neurones. Neuropharmacology 12:1073–1080
Starke K, Montel H, Gayk W, Merker R (1974) Comparison of the effects of clonidine on pre- and postsynaptic adrenoceptors in the rabbit pulmonary artery. Naunyn-Schmiedeberg's Arch Pharmacol 285:133–150
Steppeler A, Döring C, Hedler L, Starke K (1982) Effect of amezinium on the release and catabolism of 3H-monoamines in brain slices. Biochem Pharmacol 31:2395–2402
Timmermans PBMWM, van Zwieten PA (1982) 331-2: Classification, localization, mechanisms, and targets for drugs. J Med Chem 25:1389–1401
Vaatstra WJ, Deiman-van Aalst WMA, Eigemann L (1981) DU 24565, a quipazine derivative, a potent selective serotonin uptake inhibitor. Eur J Pharmacol 70:195–202
Verbeuren TJ, Coen EP, Schoups A, Van de Velde R, Baeyens R, De Potter WP (1984) Presynaptic serotonin receptors regulate the release of 3H-serotonin in hypotalamic slices of the rabbit. Naunyn-Schmiedeberg's Arch Pharmacol 327:102–106
Waldmeier PC, Baumann PA, Hauser K, Maitre L, Storni A (1982) Oxaprotiline, a noradrenaline uptake inhibitor with an active and an inactive enantiomer. Biochem Pharmacol 31:2169–2176
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Limberger, N., Bonanno, G., Späth, L. et al. Autoreceptors and α2-adrenoceptors at the serotonergic axons of rabbit brain cortex. Naunyn-Schmiedeberg's Arch. Pharmacol. 332, 324–331 (1986). https://doi.org/10.1007/BF00500082
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DOI: https://doi.org/10.1007/BF00500082