Summary
The interaction between clonidine, as an agonist at the α2-autoreceptors regulating noradrenaline release, and inhibitors of noradrenaline neuronal uptake was investigated in superfused synaptosomes, i.e. in conditions preventing accumulation of the released transmitter in the vicinity of presynaptic autoreceptors. Desipramine or cocaine did not decrease the inhibitory action of clonidine on the release of 3H-noradrenaline evoked by 15 mM KCl from rat cortex synaptosomes, even when the concentration ratio between uptake inhibitor and clonidine was very high. The present results do not support either the hypothesis of an interaction between imidazolines and noradrenaline uptake inhibitors at the level of α2-autoreceptors, or that of a functional coupling between presynaptic α2-autoreceptors and noradrenaline uptake mechanism.
This is a preview of subscription content, log in via an institution to check access.
References
Bradford MM (1976) Rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Cubeddu LX, Hoffman IS, James MK (1983) Frequency-dependent effects of neuronal uptake inhibitors on the autoreceptor-mediated modulation of dopamine and acetylcholine release from the rabbit striatum. J Pharmacol Exp Ther 226:88–94
Galzin AM, Dubocovich ML, Langer SZ (1982) Presynaptic inhibition by dopamine receptor agonists of noradrenergic neurotransmission in the rabbit hypothalamus. J Pharmacol Exp Ther 221:461–471
Göthert M, Schlicker F, Köstermann F (1983) Relationship between transmitter uptake inhibition and effects of α-adrenoceptor agonists on serotonin and noradrenaline release in the rat brain cortex. Naunyn-Schmiedeberg's Arch Pharmacol 322:121–128
Gray EG, Whittaker VP (1962) The isolation of nerve endings from brain: an electron microscope study of cell fragments derived by homogenization and centrifugation. J Anat 96:79–87
Langer SZ, Dubocovich ML (1981) Cocaine and amphetamine antagonize the decrease of noradrenergic neurotransmission elicited by oxymetazoline but potentiate the inhibition by α-methylnorepinephrine in the perfused cat spleen. J Pharmacol Exp Ther 216:162–171
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
Medgett IC, McCulloch MW, Rand MJ (1978) Partial agonist action of clonidine on prejunctional and postjunctional α-adrenoceptors. Naunyn-Schmiedeberg's Arch Pharmacol 304: 215–221
Pelayo F, Dubocovich ML, Langer SZ (1980) Inhibition of neuronal uptake reduces the presynaptic effects of clonidine but not of α-methylnoradrenaline on the stimulation-evoked release of 3H-noradrenaline from rat occipital cortex slices. Eur J Pharmacol 64:143–155
Raiteri M, Angelini F, Levi G (1974) A simple apparatus for studying the release of neurotransmitters from synaptosomes. Eur J Pharmacol 25:411–414
Raiteri M, del Carmine R, Bertollini A, Levi G (1977) Effect of desmethylimipramine on the release of [3H]-norepinephrine induced by various agents in hypothalamic synaptosomes. Mol Pharmacol 13:746–788
Raiteri M, Levi G (1978) Release mechanisms for catecholamines and serotonin in synaptosomes. In: Ehrenpreis S, Kopin I (eds) Reviews of neuroscience, vol III. Raven Press, New York, pp 77–130
Reichenbacher D, Reimann W, Starke K (1982) α-Adrenceptor-mediated inhibition of noradrenaline release in rabbit brain cortex slices. Receptor properties and role of the biophase concentration of noradrenaline. Naunyn-Schmiedeberg's Arch Pharmacol 319:71–77
Smith JE, Lane JD, Shea PA, McBride WJ, Aprison MH (1975) a method for concurrent measurement of picomole quantities of acetylcholine, choline, dopamine, norepinephrine, serotonin, 5-hydroxytryptophan, 5-hydroxyindoleacetic acid, tryptophan, tyrosine, glycine, aspartate, glutamate, alanine and gammaaminobutyric acid in single tissue samples from different areas of rat central nervous system. Anal Biochem 64:149–169
Starke K (1972) Alpha sympathomimetic inhibition of adrenergic and cholinergic transmission in the rabbit heart. Naunyn-Schmiedeberg's Arch Pharmacol 274:18–45
Starke K, Montel H (1973a) Involvement of α-receptors in clonidine-induced inhibition of transmitter release from central monoamine neurones. Neuropharmacology 12:1073–1080
Starke K, Montel H (1973b) Alpha-receptor-mediated modulation of transmitter release from central noradrenergic neurones. Naunyn-Schmiedeberg's Arch Pharmacol 279:53–60
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Maura, G., Pittaluga, A., Ricchetti, A. et al. Noradrenaline uptake inhibitors do not reduce the presynaptic action of clonidine on 3H-noradrenaline release in superfused synaptosomes. Naunyn-Schmiedeberg's Arch. Pharmacol. 327, 86–89 (1984). https://doi.org/10.1007/BF00504997
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00504997