Ontogenesis of Enzyme Systems Deaminating Different Monoamines

Abstract

I A detailed investigation into the postnatal development of the activity of the enzyme monoamine oxidase (MAO) in the rat and domestic pig was carried out. 2 MAO activity was measured in littermate male rats aged between 3 and 122 days belonging to six breeding colonies. The tissues studied were three brain regions in which monoamines may play a role in neuronal transmission (septum, hypothalamus, corpus striatum) and, for comparison, in the cerebellum. Liver, heart and adrenal glands were the peripheral organs studied. The following substrates were used to measure MAO activity in each tissue homogenate: kynuramine, tyramine, dopamine, tryptamine and 5-hydroxytryptamine (5-HT). 3 MAO activity towards kynuramine, tyramine and dopamine increased after birth in all brain regions and also in the liver, to reach maximal values between days 40 and 80. In the heart and the adrenal glands enzyme activity remained low up to 30-40 days and then increased steeply. This was the case in all litters examined. 4 All tissues deaminated more tyramine than dopamine. In the liver, the ratio of the quantities of tyramine deaminated/dopamine deaminated was approx. 2 at all ages. In the homogenates of whole brains (including or excluding the hypothalamus and striatum) this ratio was also 2 at all ages. In contrast in the isolated striatum and hypothalamus it was first much higher and reached a value of 2 only at an age of about 20 days. This may indicate an independent development of a dopamine and a tyramine deaminating enzyme system in discrete brain regions. It was suggested, that the low ability to deaminate dopamine in discrete brain regions may be due to the local presence of an enzyme inhibitor which becomes too diluted to be active in homogenates of whole brain. 5 Deamination of tryptamine in the striatum decreased between day 5 and 20 in 3 out of 4 colonies tested. There was a large fall in the deamination of 5-HT in all tissues of one group of rats, but in another 4 groups the tissues of the 5 day old rats deaminated smaller amounts of 5-HT than those of the older rats. 6 Purified hypothalamic mitochondria from 40 day old rats deaminated more tyramine and dopamine but not tryptamine per mg protein than those from 5 day old rats. 7 In the domestic pig there was a significant rise in the values in hippocampal MAO activity towards dopamine and tyramine from the foetus (55 day gestation) to the 1 week old piglet. A further steady rise up to week 6 was indicated, but this rise was not statistically significant. The difference between rat and pig probably reflected the much higher degree of maturity of the latter at birth. 8 In the hippocampus of the pig the ratio between the amount of tyramine deaminated/dopamine deaminated decreased from > 10 (foetus) to 4.8 in the 6 week old pig and 2 in the adult.

Ontogenesis of Uptake and Deamination of 5‐hydroxytryptamine, Dopamine and Β‐phenylethylamine in Isolated Perfused Lung and Lung Homogenates From Rats

“…This completely independent development of MAO deaminating 5-HT and PEA confirms the existence of A and B forms of MAO in lung. The observation that in lung, MAO activity metabolizing PEA increased up to 80 days is in contrast to results in most other organs, but agrees with MAO activity in rat heart which did not reach maximum values by the end of the 4th month of development (Blatchford et al, 1976). These results also suggest that in lung, dopamine is a substrate for MAO-B in younger animals up to 20 days old and becomes a substrate also for MAO-A in older animals.…”

“…BJP 72:4 J Discussion Age-dependent changes in uptake of amines (Kirksey & Slotkin, 1980) and in MAO activity (Blatchford et al, 1976) in various tissues of the rat have been reported. Our results have shown that in lung, uptake and MAO activity also changed with age and thus lung responds like other tissues.…”

“…Age-dependent changes in monoamine oxidase (MAO) activity in various tissues of rat and other species, including man (Blatchford, Holzbauer, Grahame-Smith & Youdim, 1976; and in uptake of monoamines (Nomura, Naitoh & Segawa, 1972;Kirksey & Slotkin, 1979) have been described. In none of these studies was the lung investigated.…”

Developmental Aspects of the Monoamine-Degrading Enzyme Monoamine Oxidase

“…Furthermore, the rates of recovery of the two forms after inhibi tion by pargyline were found to be similar [5]. The data obtained by Blatchford et al [10] on the ontogenesis of liver MAO in rats from var ious breeding colonies also suggested that the proportions of the two forms do not change with age. However, in contrast to the results of Mantle et al [14], these workers reported that age resulted in increased liver MAO ac tivities independently of the substrate used.…”

“…Lyles and Callingham [6] have shown that although tyramine is a good substrate for both forms of MAO it is metabolized essen tially only by MAO-A in the rat heart. Accord ing to this results, the data of Blatchford et al [10] showing an increase in heart MAO activ ity between day 5 and day 80 after birth in male Wistar rats from different breeding colo nies when tyramine is used as substrate can be interpreted as an increase in MAO-A activity. The same authors found contradictory results when 5-HT was used as substrate, with heart 5-HT-metabolizing activity decreasing steep ly between day 5 and day 40 in one of the breeding colonies studied.…”