STUDIES ON THE METABOLISM OF CATECHOLAMINES IN THE CENTRAL NERVOUS SYSTEM OF THE MOUSE

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Abstract
1 The distribution of the metabolites of noradrenaline, 1-(3,4-dihydroxyphenyl)ethane-1,2-diol (DOPEG) and 1-(4-hydroxy-3-methoxyphenyl)ethane-1,2-diol (MOPEG), in the brain of the mouse has been investigated. 2 The rate of disappearance of the metabolites after inhibition of the enzyme monoamine oxidase has been used to estimate their turnover rates in the mouse hypothalamus. It was concluded that the turnover of DOPEG was much faster than that of MOPEG. 3 When mice were treated with reserpine dissolved in 5% ascorbic acid solution there was an increase in the hypothalamic concentration of both MOPEG and DOPEG. However, similar increases in the concentrations of the two metabolites were seen when the animals were treated with 5% ascorbic acid solution alone. 4 The administration of tropolone, an inhibitor of the enzyme catechol-O-methyl transferase, resulted in an increase in the concentration of DOPEG. 5 Mice, exposed to a temperature of −15° C showed increased hypothalamic concentrations of both DOPEG and MOPEG. 6 The rates of formation in the mouse striatum of 3,4-dihydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3-methoxyphenylacetic acid (HVA), acidic metabolites of dopamine, were compared with the turnover rate of dopamine, estimated from the rate at which this catecholamine disappears after treatment with α-methyl-p-tyrosine. It was concluded that the estimate of dopamine turnover obtained by this method is likely to be too large because of the compensatory feedback mechanism which is thought to play a role in the metabolism of dopamine in the brain.