Increased monoamine oxidase activity following repeated electroshock seizures

W e H ave recently reported that chronic electroconvulsive seizures (ECS) lead to a long-lasting increase (up to 6 weeks) in the activity of monoamine oxidase (MAO) in the brain of rats (P ryor and O tis , 1970). Other investigators have shown increased levels of norepinephrine (NE) and 5-HT, more rapid clearance of intracisternally-injected [³H]HNE (K ety , J avoy , T hierry , J ulou and G lowinski , 1967), and increased tyrosine hydroxylase activity (M usacchio , J ulou , K ety and G lowinski , 1969) at 24 h after a series of two ECS daily for 7 days. Together, these data suggest a sustained activation of the 5-HT and/or NE systems following chronic ECS. We now report the results of a series of experiments in which some of the potential variables that may be involved in the MAO response were investigated and that indicate some biochemical specificity of the response. In these experiments, succinate dehydrogenase (SDH) activity was also assayed to assess possible nonspecific effects of repeated seizures on mitochondrial metabolism and catechol O -methyltransferase (COMT) activity was determined to see if this extracellular degradative enzyme for NE was affected in the same way as MAO located intracellularly in the mitochondria.     

Increased human platelet monoamine oxidase activity during lithium carbonate therapy

Human platelet monoamine oxidase (MAO) activity was assessed, using benzylamine C¹⁴ as the substrate, in ten patients who received a trial of lithium carbonate treatment. In all ten patients there was an increase of the median MAO activity during the lithium treatment period in comparison to the median MAO activity during a placebo treatment period. This increase in platelet MAO activity is consistent with reports by other investigators that lithium treatment is associated with increased oxidative deamination of monoamines in both animals and humans.     

Increased activity of brain and platelet monoamine oxidase in dementia of Alzheimer type

Two groups of patients with dementia of Alzheimer type were studied with respect to monoamine oxidase (MAO) activity. In one group of 11 patients MAO activity was determined in platelets and in the other group of 14 patients in the brain (hypothalamus, caudate nucleus, hippocampus and cortex gyrus cinguli) post mortem. The results were compared to controls matched for age and sex. Platelet MAO activity was significantly higher in patients with dementia of Alzheimer type compared to controls. Brain MAO-B activity but not MAO-A activity was significantly higher in the dementia group in hyppocampus and cortex gyrus cinguli. In the controls there were positive correlations for MAO-B activity with age in the four brain regions, but these correlations were absent in the dementia group. This could be explained by differences in age of onset of dementia and that the disease process does not develop homogeneously in different brains.     

Influence of age on brain vascular and cardiovascular monoamine oxidase activity in the rat

Monoamine oxidase (MAO) activity in brain microvessels and cardiovascular tissues was examined in rats of different age. MAO activity continued to increase with age in the heart, but in contrast, reached maximum activity in three weeks in the aorta, mesenteric artery and mesenteric vein. Between 7 and 60 weeks, there was a small decline in the MAO activity in the testicular artery. The highest MAO activity was found in the cerebral microvessels and increased with age. The half-life of MAO was estimated in the heart and peripheral blood vessels in young and old animals. The half-life of cardiac MAO was increased with age whereas that of the mesenteric vein, mesenteric artery and aorta remained constant between 7 and 112 weeks. Thus an explanation for this increased cardiac MAO activity in old rats was a reduced rate of degredation of this enzyme. The high activity of the enzyme in the brain microvessels suggests that it may participate in regulating the influx and efflux of monoamines in the central nervous system.     

Cellular localization of monoamine oxidase A and B in human tissues outside of the central nervous system

We studied the localization of monoamine oxidase (MAO) A and B in human heart, liver, duodenum, blood vessels and kidney by immunohistochemistry. The primary antibodies used were mouse monoclonal anti-human MAO-A (6G11/E1) and anti-human MAO-B (3F12/G10/2E3). Samples were obtained from six routine autopsy cases and fixed in 2% paraformaldehyde. All cardiomyocytes and hepatocytes showed MAO-A and MAO-B immunoreactivity. In the duodenum, both immunoreactivities were present in all cells of the villi, Lieberkühn crypts, muscularis mucosae and muscular layers, whereas Brunner glands were devoid of MAO-A and MAO-B staining. Endothelial cells of lymphatic vessels showed MAO-A but no MAO-B immunoreactivity, whereas arteries and veins presented MAO-A and MAO-B staining in muscular layers and fibroblasts but not in endothelial cells. In the kidney, renal tubuli showed MAO-A and MAO-B immunoreactivities, whereas collecting ducts and the Bowman's capsule showed only MAO-A staining. These data represent the first study of the cellular distribution of MAO-A and MAO-B in these human tissues. They show that both enzymes have a widespread distribution in the human body with a matching pattern in many, but not all tissues, and with strong differences from the pattern of distribution in rodents.     

Central monoamine oxidase and phenolsulfotransferase activities in spontaneously hypertensive rats

The activities of monoamine oxidase and phenolsulfotransferase in the hypothalamus and anterior pituitary gland of spontaneously hypertensive rats and the normotensive control (Wistar Kyoto rat) rats were investigated. The monoamine oxidase activity (determined using dopamine as substrate) in both these tissues was not significantly different between the normo- and hypertensive animals. Hypothalamic phenolsulfotransferase does not sulfate-conjugate dopamine at pH of 6.5 and pituitary phenolsulfotransferase does not sulfate-conjugate dopamine or 3,4-dihydroxyphenylacetic acid at the same pH. Hypothalamic phenolsulfotransferase activity determined using 3,4-dihydroxyphenylacetic acid as substrate was significantly higher in the spontaneously hypertensive than the Wistar Kyoto rats, while pituitary enzyme (determined using phenol as substrate) was the same in both strains of animals. We proposed that in the spontaneously hypertensive rats the higher level of hypothalamic phenolsulfotransferase could (by removing 3,4-dihydroxyphenylacetic acid as sulfated acid) increase the deamination of dopamine by monoamine oxidase. This could in turn result in the presence of high amount of sulfated 3,4-dihydroxyphenylacetic acid in the anterior pituitary gland reported in our earlier study, and be partly responsible for the reduced central dopaminergic activity found in the hypertensive rats.     

Increased monoamine oxidase activity and imidazoline binding sites in insulin-resistant adipocytes from obese Zucker rats

BACKGROUND Despite overt insulin resistance,adipocytes of genetically obese Zucker rats accumulate the excess of calorie intake in the form of lipids.AIM To investigate whether factors can replace or reinforce insulin lipogenic action by exploring glucose uptake activation by hydrogen peroxide,since it is produced by monoamine oxidase(MAO)and semicarbazide-sensitive amine oxidase(SSAO)in adipocytes.METHODS 3H-2-deoxyglucose uptake(2-DG)was determined in adipocytes from obese and lean rats in response to insulin or MAO and SSAO substrates such as tyramine and benzylamine.14C-tyramine oxidation and binding of imidazolinic radioligands[3H-Idazoxan,3H-(2-benzofuranyl)-2-imidazoline]were studied in adipocytes,the liver,and muscle.The influence of in vivo administration of tyramine+vanadium on glucose handling was assessed in lean and obese rats.RESULTS 2-DG uptake and lipogenesis stimulation by insulin were dampened in adipocytes from obese rats,when compared to their lean littermates.Tyramine and benzylamine activation of hexose uptake was vanadate-dependent and was also limited,while MAO was increased and SSAO decreased.These changes were adipocyte-specific and accompanied by a greater number of imidazoline I2 binding sites in the obese rat,when compared to the lean.In vitro,tyramine precluded the binding to I2 sites,while in vivo,its administration together with vanadium lowered fasting plasma levels of glucose and triacylglycerols in obese CONCLUSION The adipocytes from obese Zucker rats exhibit increased MAO activity and imidazoline binding site number.However,probably as a consequence of SSAO down-regulation,the glucose transport stimulation by tyramine is decreased as much as that of insulin in these insulin-resistant adipocytes.The adipocyte amine oxidases deserve more studies with respect to their putative contribution to the management of glucose and lipid handling.     

Platelet monoamine oxidase activity in children and adolescents.

Platelet monoamine oxidase activity has been measured in a group of preadolescent, adolescent, and post-adolescent individuals. The platelet oxidase activity was highest in the female in all three populations examined. Children diagnosed as having primary autism did not display differences in their platelet oxidase activity as compared to children of similar age and sex.     

Increased baroreceptor response in mice deficient in monoamine oxidase A and B

The recent development of mice doubly deficient for monoamine oxidase A and B (MAO-A/B, respectively) has raised questions about the impact of these mutations on cardiovascular function, in so far as these animals demonstrate increased tissue levels of the vasoactive amines serotonin, norepinephrine, dopamine, and phenylethylamine. We recorded femoral arterial pressures and electrocardiograms in adult MAO-A/B-deficient mice during halothane-nitrous oxide anesthesia as well as 30 min postoperatively. During both anesthesia and recovery, systolic, diastolic, and mean arterial pressures were 10-15 mmHg lower in MAO-A/B-deficient mice compared with normal controls (P < 0.01). Mutants also showed a greater baroreceptor-mediated reduction in heart rate in response to hypertension after intravenous pulses of phenylephrine or angiotensin II. Tachycardia elicited in response to hypotension after nitroprusside was greater in mutants than in controls. Heart rate responsiveness to changes in arterial pressure was abolished after administration of glycopyrrolate, with no differences in this phenomenon noted between genotypes. These data suggest that prevention of hypertension may occur in chronic states of catecholaminergic/indoleaminergic excess by increased gain of the baroreflex.     

Compounds from the sea with actions on the cardiovascular and central nervous systems

Recent efforts at probing into the oceans have produced evidence that marine invertebrates such as gorgonians and sponges offer a rich reserve of pharmacologically interesting molecules. Our investigations indicate that it is possible to obtain novel compounds both structurally and pharmacologically. For example, autonomium from a sponge is a dual adrenergic combined with cholinergic molecule, with a structure that may be considered a hybrid between a catecholamine and choline. Various terpenoids and indole derivatives from marine organisms have been found to possess activities on the central nervous system. Several peptides from sea anemones are cardiotonic and have initiated a new concept of chemical structure believed to be associated with cardiac activity. A number of closely related halogenated cyclic ethers are good inhibitors of drug metabolism. Thus, there seems little doubt that the sea warrants an extensive chemical and pharmacological examination.     

Low platelet monoamine oxidase activity in cigarette smokers

The activity of platelet monoamine oxidase was found to be significantly lower in normal female subjects who smoked at least 5 cigarettes per day than in non-smokers. The platelet MAO activity of individuals who had given up smoking was not significantly different from the activity for non-smokers. The difference in activities between smokers and non-smokers, due entirely to a V_max rather than a K_m change, was not due to a direct effect of nicotine upon the platelet MAO. In addition, platelet-poor plasma from smokers activated platelet MAO in an identical manner to that from non-smokers. The significance of these results are discussed in terms of personality characteristics such as impulsivity and sensation seeking, that may be related to both smoking and to low MAO activity.