Summary
In slices of mouse hypothalamus labelled in vitro with 3H-noradrenaline (3H-NA), the deaminated metabolite 3H-3,4-dihydroxyphenylglycol (3H-DOPEG), represented 40.2±2.6% of the total outflow of radioactivity and was the main fraction in the sponteneous efflux. Inhibition of neuronal monoamine oxidase by exposure to 60 μM bretylium, reduced the outflow of 3H-DOPEG to 9.7±0.3%. At the same time, the proportion of 3H-normetanephrine (3H-NMN) was significnatly increased. On the other hand, an increased outflow of 3H-DOPEG and a lower proportion of 3H-NMN was obtained in the presence of 2.9 μM of the reserpine like agent Ro 4-1284.
It is suggested that in the mouse hypothalamus, the deaminated metabolite, DOPEG, is formed inside the nerve terminals, while the O-methylated metabolite, NMN, might result from the activity of extraneuronal catechol O-methyltransferase.
References
Adler-Graschinsky, E., Langer, S. Z., Rubio, M. C.: Metabolism of norepinephrine released by phenoxybenzamine in isolated guinea-pig atria. J. Pharmacol. Exp. Ther. 180, 286–301 (1972)
Braestrup, C., Nielsen, M.: Intra and extraneuronal formation of the two major noradrenaline metabolites in the cns of rats. J. Pharm. Pharmacol. 27, 413–419 (1975)
Ceasar, P. M., Hague, P., Sharman, D. F., Werdinius, B.: Studies on the metabolism of catecholamines in the central nervous system of the mouse. Br. J. Pharmacol. 51, 187–195 (1974)
Farah, M. B., Adler-Graschinsky, E., Langer, S. Z.: Possible physiological significance of the initial step in the catabolism of noradrenaline in the central nervous system of the rat. Naunyn-Schmiedeberg's Arch. Pharmacol. 297, 119–131 (1977)
Furchgott, R. F., Sanchez, Garcia P., Wakade, A. R., Cervoni, P.: Interactions of bretylium and other drugs on guinea-pig atria: evidence for inhibition of neuronal monoamine oxidase by bretylium. J. Pharmacol. Exp. Ther. 179, 171–185 (1971)
Graefe, K. H., Stefano, F. J. E., Langer, S. Z.: Preferential metabolism of (−)-3H-noradrenaline through the deaminated glycol in the rat vas deferens. Biochem. Pharmacol. 22, 1147–1160 (1973)
Howlett, D. R., Jenner, F. A., Nahorski, S. R.: Urinary 3-methoxy-4-hydroxyphenylglycol production in mice and rats following intraventricular 6-hydroxydopamine. J. Pharm. Pharmacol. 27, 447–449 (1975)
Langer, S. Z.: Selective metabolic pathways for noradrenaline in the peripheral and in the central nervous system. Med. Biol. 52, 372–383 (1974)
Laverty, R., Taylor, K. M.: The fluorimetric assay of catecholamines and related compounds: Improvements and extensions to the hydroxyindole technique. Anal. Biochem. 22, 269–279 (1968)
Moquilevsky, J. A., Rubinstein, L.: Glycolytic and oxidative metabolism of hypothalamic areas in prepuberal androgenized rats. Neuroendocrinology 2, 213–221 (1967)
Snedecor, G. W., cochran, W. G.: Statistical Methods, 6th ed., Ames: The Iowa State University Press 1967
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Adler-Graschinsky, E. Metabolic fate of 3H-noradrenaline released from the mouse hypothalamus. Naunyn-Schmiedeberg's Arch. Pharmacol. 302, 337–339 (1978). https://doi.org/10.1007/BF00508305
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00508305