Summary
The effect of the dopamine-β-hydroxylase inhibitor bis-(4-methyl-1-homopiperazinylthiocarbonyl)-disulphide (FLA-63) on the release of dopamine and noradrenaline was studied in regions of the rat central nervous system rich in dopamine or noradrenaline nerve terminals. The release was investigated by analyzing the accumulation of the 3-0-methylated catecholamines after inhibition of the monoamine oxidase by nialamide. In the dopamine-rich corpus striatum, the concentration of dopamine was unchanged but its release was enhanced after treatment with FLA-63. The noradrenaline concentration and release were markedly reduced. In the areas containing mainly noradrenaline nerve terminals, dopamine accumulated but did not stoichiometrically replace the missing noradrenaline. There was a pronounced release of dopamine from the noradrenaline nerves after the dopamine-β-hydroxylase inhibiticn. This release may, at least partly, explain why noradrenaline is not stoichiometrically replaced by dopamine.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Andén, N.-E., K. Fuxe, B. Hamberger, andT. Hökfelt: A quantitative study on the nigro-neostriatal dopamine neuron system in the rat. Acta physiol. scand.67, 306–312 (1966).
Andén, N.-E., andT. H. Svensson: Release of dopamine from central noradrenaline nerves after treatment with reserpine plus amphetamine. J. Neural Transmission34, 23–30 (1973).
Atack, C. V.: The determination of dopamine by a modification of the dihydroxyindole fluorimetric assay. Br. J. Pharmacol. (in preparation, 1973).
Atack, C. V., andT. Magnusson: Individual elution of noradrenaline (together with adrenaline), dopamine, 5-hydroxytryptamine and histamine from a single, strong cation exchange column, by means of mineral acid-organic solvent mixtures. J. Pharm. Pharmacol.22, 625–627 (1970).
Axelrod, J.: Methylation reactions in the formation and metabolism of catecholamines and other biogenic amines. Pharmacol. Rev.18, 95–113 (1966).
Besson, M.-J., A. Cheramy, P. Feltz, andJ. Glowinski: Dopamine: spontaneous and drug-induced release from the caudate nucleus in the cat. Brain Res.32, 407–424 (1971).
Carlsson, A.: Discussion. In: Adrenergic Mechanisms, pp. 558–559. London: Churchill. 1960.
Carlsson, A., K. Fuxe, andT. Hőkfelt: Failure of dopamine to accumulate in central noradrenaline neurons after depletion with diethyldithiocarbamate. J. Pharm. Pharmacol.19, 481–483 (1967).
Carlsson, A., andM. Lindqvist: A method for the determination of normetanephrine in brain. Acta physiol. scand.54, 83–86 (1962).
Carlsson, A., andB. Waldeck: A method for the fluorimetric, determination of 3-methoxytyramine in tissues and the occurrence of this amine in brain. Scand. J. clin. Lab. Invest.16, 133–138 (1964).
Corrodi, H., K. Fuxe, B. Hamberger, andA. Ljungdahl: Studies on central and peripheral noradrenaline neurons using a new dopamine-β-hydroxylase inhibitor. Eur. J. Pharmacol.12, 145–155 (1970).
Florvall, L., andH. Corrodi: Dopamine-―-hydroxylase inhibitors. Acta pharmaceut. scand.7, 7–22 (1970).
Fuxe, K.: Evidence for the existence of monoamine neurons in the central nervous system. IV. The distribution of monoamine nerve terminals in the central nervous system. Acta physiol. scand.64, Suppl. 247, 37–85 (1965).
Häggendal, J.: An improved method for fluorimetric determination of small amounts of adrenaline and noradrenaline in plasma and tissues. Acta physiol. scand.59, 242–254 (1963).
Kopin, I. J., G. R. Breese, K. R. Krauss, andV. K. Weise: Selective release of newly synthesized norepinephrine from the cat spleen during sympathetic nerve stimulation. J. Pharmacol. exp. Ther.161, 271–278 (1968).
Musacchio, J. M., J. E. Fischer, andI. J. Kopin: Subcellular distribution and release by sympathetic nerve stimulation of dopamine and α-methyl dopamine. J. Pharmacol. exp. Ther.152, 51–55 (1966).
Musaccbio, J. M., I. J. Kopin, andV. K. Weise: Subcellular distribution of some sympathomimetic amines and theirβ-hydroxylated derivatives in the rat heart. J. Pharmacol. exp. Ther.148, 22–28 (1965).
Nybäck, H.: Regional disappearance of catecholamines formed from 14C-tyrosine in rat brain. Effect of synthesis inhibitors and chlorpromazine. Acta pharmacol. toxicol.30, 372–384 (1971).
Schanberg, S. M., J. J. Schildkraut, G. R. Breese, andI. J. Kopin: Metabolism of normetanephrine-H3 in rat brain —identification of conjugated 3-methoxy-4-hydroxyphenylglycol as the major metabolite. Biochem. Pharmacol.17, 247–254 (1968).
Svensson, T. H.: Increased dopamine concentration in the striatum in the mouse by FLA-63, a dopamine-β-hydroxylase inhibitor. J. Pharm. Pharmacol.25, 73–75 (1973).
Svensson, T. H., andB. Waldeck: On the significance of central noradrenaline for motor activity: experiments with a new dopamine-β-hydroxylase inhibitor. Eur. J. Pharmacol.7, 278–282 (1969).
Thoenen, H., W. Haefely, K. F. Gey, andA. Hürlimann: Diminished effects of sympathetic nerve stimulation in cats pretreated with disulfiram; liberation of dopamine as sympathetic transmitter. Life Sci.4, 2033–2038 (1965).
Thoenen, H., W. Haefely, K. F. Gey, andA. Hürlimann: Quantitative aspects of the replacement of norepinephrine by dopamine as a sympathetic transmitter after inhibition of dopamine-β-hydroxylase by disulfiram. J. Pharmacol. exp. Ther.156, 246–251 (1967).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Andén, N.E., Atack, C.V. & Svensson, T.H. Release of dopamine from central noradrenaline and dopamine nerves induced by a dopamine-β-hydroxylase inhibitor. J. Neural Transmission 34, 93–100 (1973). https://doi.org/10.1007/BF01244662
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF01244662