Summary
A number of drugs were tested in histochemical studies using a fluorescent technique in order to establish whether they inhibited the uptake ofα-methylnoradrenaline in catecholamine neurones in the reserpine-treated rat in vivo. The noradrenaline axons in the iris, mesenteric veins, and vas deferens were investigated, as well as the dopamine axons of the eminentia mediana of the hypothalamus. In the noradrenaline neurones an inhibitory action was exerted by the following substances (listed in descending order of effectiveness): desipramine, guanethidine, methylphenidate, cocaine, 1-(3-methylaminopropyl)-dibenzo [b, e] bicyclo [2.2.2] octadiene (34′276-Ba, a new antidepressive from the series of the dibenzo-bicyclo-octadienes), and tripelennamine. Of these substances only methylphenidate, cocaine, and tripelennamine exerted an inhibitory effect in the dopamine neurones. Two other compounds that were studied, the psycho-active drug benz-octamine (a tranquillizer from the series of the dibenzo-bicyclo-octadienes) and the monoamine oxidase inhibitor N-methyl-N-(2-propynyl)-1-indanamme (11′739-Su) did not exert an inhibitory effect either in the noradrenaline or in the dopamine neurones. Possible correlations between apparent inhibition of uptake and depletion ofα-methylnoradrenaline are discussed.
Zusammenfassung
Die Hemmwirkung verschiedener Pharmaka auf die Aufnahme vonα-Methylnoradrenalin (MNA) in Katecholamin-Neuren wurde fluorescenz-histochemisch an der reserpinisierten Ratte in vivo untersucht. Geprüft wurden die Noradrenalin-Axone in Iris, Mesenterialvenen und Vas deferens sowie die Dopamin-Axone der Eminentia mediana des Hypothalamus. In den Noradrenalin-Neuren hemmen mit abnehmender Wirksamkeit folgende Substanzen: Desipramin, Guanethidin, Methylphenidat, Cocain, 1-(3-Methylaminopropyl)-dibenzo [b, e] bioyclo [2.2.2] octadien (34′276-Ba, ein neues Antidepressivum aus der Reihe der Dibenzo-bicyclo-octadiene) und Tripelennamin. In den Dopamin-Neuren hemmen von diesen Substanzen nur Methylphenidat, Cocain und Tripelennamin. Zwei weitere untersuchte Verbindungen, das Psychopharmakon Benzoctamin (ein Tranquillizer aus der Reihe der Dibenzo-bicyclo-octadiene) und der Monoaminoxydasehemmer N-methyl-N-(2-propinyl)-1-indanamin (11′739-Su) hemmen weder in den Noradrenalin- noch in den Dopamin-Neuren. Mögliche Beziehungen zwischen apparenter Aufnahmehemmung und Entleerung von MNA werden diskutiert.
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Abbreviations
- NA:
-
Noradrenalin
- DA:
-
Dopamin
- MNA:
-
α-Methylnor-adrenalin
- Dopa:
-
3,4-Dihydroxyphenylalanin
- KA:
-
Katecholamin(e)
- ZNS:
-
Zentralnervensystem
- i.p.:
-
intraperitoneal
- i.v.:
-
intravenös
Literatur
Bein, H. J., Maître, L.: Unveröffentlichte Resultate.
- Wilhelm, M.: Unveröffentlichte Resultate.
Blaschko, H., Richter, D., Schlossmann, H.: The oxidation of adrenaline and other amines. Biochem. J.31, 2187 (1937).
Carlsson, A., Dahlström, A., Fuxe, K., Hillarp, N. Å.: Failure of reserpine to deplete noradrenaline neurons ofα-methyl-noradrenaline formed fromα-methyl-dopa. Acta pharmacol. (Kbh.)22, 270 (1965).
—, Fuxe, K., Hamberger, B., Lindquist, M.: Biochemical and histochemical studies on the effects of imipramine-like drugs and (+)-amphetamine on central and peripheral catecholamine neurons. Acta physiol. scand.67, 481 (1966).
—, Lindquist, M., Fuxe, K., Hamberger, B.: The effect of (+)-amphetamine on various central and peripheral catecholamine-containing neurons. J. Pharm. Pharmacol.18, 128 (1966).
—, Lundborg, P., Stitzel, R., Waldeck, B.: Uptake, storage and release of H3-α-methyl-norepinephrine. J. Pharmacol. exp. Ther.158, 175 (1967).
Corrodi, H., Jonsson, G.: The formaldehyde fluorescence method for the histochemical demonstration of biogenic monoamines. A review on the methodology. J. Histochem. Cytochem.15, 65 (1967).
— —, Malmfors, T.: Factors affecting the quality and intensity of the fluorescence in the histochemical method of demonstration of catecholamines. Acta histochem. (Jena)25, 367 (1966).
—, Malmfors, T., Sachs, Ch.: Differences in the uptake of secondary catechol-amines by the adrenergic nerves. Acta physiol. scand.67, 358 (1966).
Dahlström, A., Fuxe, K.: Evidence for the existence of monoamine-containing neurons in the central nervous system: I Demonstration of monoamines in the cell bodies of brain stem neurons. Acta physiol. scand.62, Suppl. 232 (1964).
Falck, B.: Observations on the possibilities of the cellular localization of monoamines by a fluorescence method. Acta physiol. scand.56, Suppl. 197 (1962).
—, Hillarp, N.-Å., Thieme, G., Torp, A.: Fluorescence of catecholamines and related compounds condensed with formaldehyde. J. Histochem. Cytochem.10, 348 (1962).
Ferry, C. B.: The autonomic nervous system. Ann. Rev. Pharmacol.7, 185 (1967).
Fuxe, K.: Evidence for the existence of monoamine neurons in the central nervous system. IV Distribution of monoamine nerve terminals in the central nervous system. Acta physiol. scand.64, Suppl. 247 (1965).
—, Hamberger, B., Malmfors, T.: Inhibition of amine uptake in tubero-in-fundibular dopamine neurons and in catecholamine cell bodies of the area postrema. J. Pharm. Pharmacol.18, 543 (1966).
— — —: The effect of drugs on accumulation of monoamines in tubero-in-fundibular dopamine neurons. Europ. J. Pharmacol.1, 334 (1967).
—, Hillarp, N.-Å.: Uptake of l-dopa and noradrenaline by central catecholamine neurons. Life Sci.3, 1403 (1964).
—, Hökfelt, T.: Further evidence for the existence of tubero-infundibular dopamine neurons. Acta physiol. scand.66, 245 (1966).
Gillespie, J. S., Kirpekar, S. M.: The inactivation of infused noradrenaline by the cat spleen. J. Physiol. (Lond.)176, 205 (1965).
Häggendal, J., Hamberger, B.: Quantitative in vitro studies on noradrenaline uptake and its inhibition by amphetamine, desipramine, and chlorpromazine. Acta physiol. scand.70, 277 (1967).
Hamberger, B.: Reserpine-resistant uptake of catecholamines in isolated tissues of the rat. A histochemical study. Acta physiol. scand.71, Suppl. 295 (1967).
—, Malmfors, T.: Uptake and release ofα-methylnoradrenaline in vitro after reserpine pretreatment. A histochemical study. Acta physiol. scand.70, 412 (1967).
—, Masuoka, D.: Localization of catecholamine uptake in rat brain slices. Acta Pharmacol. Toxicol.22, 363 (1965).
Hertting, G., Axelrod, J., Whitby, L. G.: Effect of drugs on the uptake and metabolism of H3-norepinephrine. J. Pharmacol. exp. Ther.134, 146 (1961).
Hillarp, N.-Å, Malmfors, T.: Reserpine and cocaine blocking of the uptake and storage mechanisms in adrenergic nerves. Life Sci.3, 703 (1964).
Isaac, L., Goth, A.: Interaction of antihistaminics with norepinephrine uptake: A cocaine-like effect. Life Sci.4, 1899 (1965).
Iversen, L. L.: The uptake of noradrenaline by the isolated perfused rat heart. Brit. J. Pharmacol.21, 523 (1963).
—: The inhibition of noradrenaline uptake by drugs. Advanc. Drug. Res.2, 5 (1965).
—: The uptake and storage of noradrenaline in sympathetic nerves. Cambridge: University Press 1967.
Johnson, G. L., Kahn, J. B., jr.: Cocaine and antihistaminic compounds: comparison of effects of some cardiovascular actions of norepinephrine, tyramine and bretylium. J. Pharmacol. exp. Ther.152, 458 (1966).
Jonsson, G.: Fluorescence methods for the histochemical demonstration of monoamines. VII. Fluorescence studies on biogenio monoamines and related compounds condensed with formaldehyde. Histochemie8, 288 (1967).
Lichtensteiger, W., Langemann, H.: Uptake of exogenous catecholamines by monoamine-containing neurons of the central nervous system: uptake of catecholamines by arcuato-infundibular neurons. J. Pharmacol. exp. Ther.151, 400 (1966).
—, Mutzner, U., Langemann, H.: Uptake of 5-hydroxytryptamine and 5-hydroxy-tryptophan by neurons of the central nervous system normally containing catecholamines. J. Neurochem.14, 489 (1967).
Lundborg, P.: Studies on the uptake and subcellular distribution of catechol-amines and theirα-methylated analogues. Acta physiol. scand.72, Suppl. 302 (1967).
Maître, L.: Monoamine oxidase inhibiting properties of Su-11′739 in the rat. Comparison with pargyline, tranylcypromine and iproniazid. J. Pharmacol. exp. Ther.157, 81 (1967).
Malmfors, T.: Studies on adrenergic nerves. The use of rat and mouse iris for direct observations on their physiology and pharmacology at cellular and subcellular levels. Acta physiol. scand.64, Suppl. 248 (1965).
—: Fluorescent histochemical studies on the uptake, storage, and release of catecholamines. Amer. Heart Ass. Monograph No.17, III, 25 (1967).
Maxwell, R. A.: Concerning the mechanism of action of methylphenidate on the responses of rabbit vascular tissue to norepinephrine. J. Pharmacol. exp. Ther.147, 289 (1965).
—, Sylwestrowicz, H. D., Holland, R., Schneider, F., Daniel, A. J.: Some actions of methylphenidate on the vascular system, arterial tissue and the nictitating membrane. J. Pharmacol. exp. Ther.131, 355 (1961).
Montanari, R., Costa, E., Beaven, M. A., Brodie, B. B.: Turnover rates of norepinephrine in hearts of intact mice, rats, and guinea pigs using tritiated norepinephrine. Life Sci.2, 232 (1963).
Povalski, H. J., Goldsmith, E. D.: Effect of methylphenidate on cardiovascular ctions of pressor amines. Proc. Soc. exp. Biol. (N.Y.)101, 717 (1959).
Rinne, U. K., Sonninen, V.: The occurrence of dopamine and noradrenaline in the tubero-hypophysial system. Experientia (Basel)24, 177 (1968).
Ritzén, M.: Quantitative fluorescence microspectrophotometry of catechol-amine-formaldehyde products. Model experiments. Exp. Cell. Res.44, 505 (1966).
Sjöstrand, N. O.: The adrenergic innervation of the vas deferens and the accessory male genital glands. An experimental and comparative study of its anatomical and functional organization in some mammals, including the presence of adrenaline and chromaffin cells in these organs. Acta physiol. scand.65, Suppl. 257 (1965).
Sjöstrand, N. O., Swedin, G.: Effect of reserpine on the noradrenaline content of the vas deferens and the seminal vesicle compared with the submaxillary gland and the heart of the rat. Acta physiol. scand.72, 370 (1968).
Spector, S., Melmon, K., Sjoerdsma, A.: Evidence for rapid turnover of norepinephrine in rat heart and brain. Proc. Soc. exp. Biol. (N.Y.)111, 79 (1962).
Udenfriend, S., Zaltzman-Nirenberg, P.: Norepinephrine and 3,4-dihydroxyphenethylamine turnover in guinea pig brain in vivo. Science142, 394 (1963).
Van Orden, L. S., Bensch, K. G., Giarman, N. J.: Histochemical and functional relationships of catecholamines in adrenergic nerve endings. II. Extravesicular norepinephrine. J. Pharmacol. exp. Ther.155, 428 (1967).
—, Bloom, F. E., Barrnett, R. J., Giarman, N. J.: Histochemical and functional relationships of catecholamines in adrenergic nerve endings. I. Participation of granular vesicles. J. Pharmacol. exp. Ther.154, 185 (1966).
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Lorez, H.P. Histochemische Untersuchung der Wirkung von Pharmaka auf die Aufnahme vonα-Methylnoradrenalin in Noradrenalin- und Dopamin-Neuren bei der reserpinisierten Ratte. Z. Gesamte Exp. Med. 151, 241–260 (1969). https://doi.org/10.1007/BF02044567
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DOI: https://doi.org/10.1007/BF02044567
Key-words
- Catecholamines
- Reserpine-resistant uptake of catecholamines
- Inhibition of neuronal uptake of catecholamines
- Tuberoinfundibular dopamine neurons
- Dibenzobicyclooctadien-derivates