Tissue distribution of substance P in the domestic pig during postnatal development.
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Biomedical subjects
Publications and source records attributed to M Holzbauer.
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The activities of three enzymes involved in the metabolism of neurotransmitter substances in the brain of the guinea pig were studied during gestation and the first month after birth. Monoamine oxidase (MAO) activity towards dopamine, tryptamine, 5-hydroxytryptamine and phenylethylamine in whole brain homogenates was, at day 30 of gestation, already similar to that found in the adult animal. When specific brain regions were analysed, a significant increase in enzyme activity towards dopamine, tyramine and tryptamine between day 40 and 60 of gestation became apparent. In the guinea pig, as in the rat, there appears to be a parallelism in the development of neuronal systems containing monoamines and MAO activity. Glutamate decarboxylase and choline acetyltransferase activities were trebled during the last two weeks of gestation. A further small increase to adult values occurred during the first three weeks after birth.
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The combined neural and intermediate lobes (N.I.L.) of the pituitary glands of Brattleboro rats contained significantly more noradrenaline (NA) than those of normal controls of the same age. In addition, in 4 and 6 months old rats the N.I.L. of the homozygotes (Di-rats) contained about twice as much NA as those of the heterozygotes (non-Di-rats). In the enlarged and hyperaemic neural lobes of the Di-rats enlarged blood vessels could be seen. They were surrounded by a rich network of nerve fibres which displayed catecholamine fluorescence. The NA concentrations in the medial basal hypothalamus (M.B.H.) of 4, 6, and 9 months old Di-rats were significantly higher than those of the non-Di-rats and of controls of the same age. This may contribute to the diminished ACTH secretion in Brattleboro rats. The total amount of DA contained in the N.I.L. of 9 months old Di-rats was 20% lower than in the non-Di-rats of the same age. The concentrations of homovanillic acid (HVA) in the corpora striata of 4 months old Di- and non-Di-rats was significantly higher than in older Brattleboro rats and in control rats of various strains and ages. At 9 months it was nearly twice as high in the Di-rats as in the non-Di-rats. The concentrations of dihydroxyphenylacetic acid in the striata of 4--6 months old Di- and non-Di-rats were higher than those of Long Evans rats of the same age.
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1 The reactivity of the pituitary-adrenal axis of the young pig was tested for its suitability as a sensitive index for any discomfort that might be experienced under certain conditions of intensive husbandry.2 In a thermoneutral environment, most undisturbed piglets showed only slight variations in the plasma concentrations of adrenocorticotrophic hormone (ACTH) and corticosteroids.3 Stimuli such as exposure to ambient temperatures of +40 degrees C or -5 degrees C were required to cause large rises in the plasma concentrations of ACTH and corticosteroids.4 Apparently milder stimuli, such as change of environment, slight frustration or changes in ambient temperatures between +5 degrees C and +30 degrees C only rarely caused a significant rise in plasma corticosteroids. Thus changes in plasma corticosteroid concentrations are not a sensitive index for the reaction of a piglet to its environment.5 Increases in plasma ACTH concentrations occurred faster than those of the corticosteroids, were larger when expressed as a percentage of the basal values and occurred following relatively small disturbances such as omission of the reward in an operant behaviour test when corticosteroid changes were often not detectable. Thus rises in plasma ACTH might be a useful indication that a given situation is disturbing to a pig. The reaction of plasma ACTH concentrations to chronic irritations as they might occur in intensive husbandry remains to be investigated.6 Azaperone (2 mg/kg i.m.), a drug which is used as a sedative in pigs, caused a rise of about 50% in plasma corticosteroid concentrations. It did not diminish the large steroid output seen when the animals were exposed to high and low ambient temperatures.
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This article explores the possibility that malfunction of the enzyme monoamine oxidase (E.C. 1.4.3.4., MAO) could lead to aberrations in the catabolism of biogenic amines in the central nervous system and give rise to certain mental abnormalities. No conclusive evidence could be presented to substantiate this. Data on the normal function of the enyzme (for example its existence in multiple forms, the control of MAO activity by hormones or the independent development of MAO activities towards different substrates during maturation) are reviewed.
1 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 greater than 10 (foetus) to 4.8 in the 6 week old pig and 2 in the adult.
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In the striata of litter-mate rats the development of the monoamine oxidase (MAO) activity towards dopamine in vitro followed a similar time course with age as the tissue concentrations of homovanillic acid and dihydroxphenylacetic acid, the two acid metabolites of dopamine formed by the action of MAO.