Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: HUMANGGP:001709 (MAO-A)
 2,432 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ejaculatory response and other components of the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (3 mg kg-1, i.p.) were studied following single and repeated treatment of rats with eight different monoamine oxidase (MAO) inhibitors. Single and repeated treatment with the 5-HT agonist 5-MeODMT, and with low doses of the potent releaser of 5-HT, p-chloroamphetamine (PCA) were also included in the study. Repeated but not single treatment with 5-MeODMT reduced strongly but reversibly the ejaculatory response and the behavioural responses. Repeated but not single treatment with the nonselective and irreversible MAO inhibitors nialamide and pargyline reduced markedly the ejaculatory response but only slightly the 5-HT behavioural responses. Repeated treatment with the irreversible MAO-B inhibitor (-)-deprenyl, with the irreversible MAO-A inhibitor, clorgyline, with the reversible MAO-A inhibitor moclobemide, and with low doses of PCA did not affect either of the responses. Repeated but not single combined treatment with clorgyline plus PCA caused an almost complete blockade of all the four responses. The selective and reversible MAO-A inhibitors (as well as 5-HT releasers) amiflamine, alpha-ethyltryptamine, and alpha-methyltryptamine reduced markedly the ejaculatory response after both single and repeated treatments. The behavioural responses were blocked only after repeated treatment. It is concluded that single and repeated treatments of rats with different MAO inhibitors do not produce a common alteration in 5-HT2 receptor functions. Repeated treatment with 5-MeODMT caused a blockade of 75-95% of the ejaculatory response and 5-HT behavioural responses. A similar strong blockade was only produced by the combined effect of MAO-A inhibition and 5-HT release.
 ...
PMID:The effects of monoamine oxidase inhibitors on the ejaculatory response induced by 5-methoxy-N,N-dimethyltryptamine in the rat. 309 Nov 32

The relative distribution of type A and type B monoamine oxidase (MAO) inside and outside the monoaminergic synaptosomes in preparations from hypothalamus and striatum of the guinea pig was determined by incubation of synaptosomal preparations of these regions with low concentrations of [14C]5-hydroxytryptamine (5-HT), noradrenaline, and dopamine. The deamination within the monoaminergic synaptosomes was hindered by selective amine uptake inhibitors. In the absence of these inhibitors, both intra- and extraneuronal deamination was measured. The two forms of the enzyme were differentiated with the irreversible and selective MAO-A and MAO-B inhibitors clorgyline and selegiline (l-deprenyl), respectively. [14C]5-HT was deaminated greater than 90% by MAO-A both inside and outside the 5-hydroxytryptaminergic synaptosomes prepared from the guinea pig hypothalamus. The deamination of [14C]noradrenaline within the noradrenergic synaptosomes of the hypothalamic preparation was in the ratio 75:25% for MAO-A:MAO-B; the corresponding ratio outside these synaptosomes was 45:55%. The deamination of [14C]dopamine within dopaminergic synaptosomes in the striatal preparation was 65% type A:35% type B, whereas outside these synaptosomes the ratio was 35:65%. Because the relative amounts and the distribution of the two forms of MAO in the guinea pig brain seem to be similar to those previously detected for the human brain, the MAO in the guinea pig brain may be a good model for the MAO in the human brain.
 ...
PMID:Distribution of the two forms of monoamine oxidase within monoaminergic neurons of the guinea pig brain. 309 21

The histochemical distribution of monoamine oxidase A and B in rat brain was investigated using a coupled peroxidatic technique with benzylamine and tyramine as substrates and clorgyline and (-)-deprenyl as selective inhibitors. Benzylamine oxidase was absent in all areas. Both forms of monoamine oxidase were present, at low levels, in all areas; in addition several regions showed high activity of one or other form or both. Substantial activity of monoamine oxidase B was identified in the pineal gland, the lining of the ventricles, several hypothalamic regions, and the raphe nuclei. The locus coeruleus and interpeduncular nucleus possessed considerable type A activity. The substantia nigra and striatum showed no staining above the low general level, although the ventral tegmental area showed higher levels of both A and B. In general, noradrenaline-containing neuronal cell body areas showed monoamine oxidase A, and 5-hydroxytryptamine-rich areas monoamine oxidase B. There was no consistent enrichment of either in corresponding dopamine-rich regions. Monoamine oxidase thus appears to have a different role in these three types of neuron. The low level of monoamine oxidase B in the nigrostriatal tract may help to explain the resistance of the rat to MPTP toxicity.
 ...
PMID:Histochemical localisation of monoamine oxidase A and B in rat brain. 317 72

Monoamine oxidase (MAO) was characterized in tissue homogenates from rat pancreatic islets, rat neurohypophysis and adenohypophysis, and rat and bovine adrenal medulla and adrenal cortex. Phenylethylamine was preferentially deaminated by rat pancreatic islet and bovine adrenal medulla MAO and with slight preference by rat neurohypophysis MAO, whereas 5-hydroxytryptamine was preferentially deaminated by MAO from all other endocrine tissues. Tyramine was a good substrate for all tissues. Clorgyline, a selective inhibitor of MAO-A, preferentially inhibited deamination of 5-hydroxytryptamine by all tissue homogenates, whereas deprenyl, a selective inhibitor of MAO-B, preferentially inhibited deamination of phenylethylamine. Km values for 5-hydroxytryptamine and tyramine were higher by one to two decimal powers than for phenylethylamine in homogenates from all endocrine tissues. Km values were significantly lower for 5-hydroxytryptamine and significantly higher for phenylethylamine in rat and bovine adrenal cortex than in adrenal medulla. According to these results, the contributions of MAO-B to total enzyme activity were 70% for rat pancreatic islets, 45% for rat neurohypophysis, 15% for rat adenohypophysis, 20% for rat adrenal medulla, 10% for rat adrenal cortex, 60% for bovine adrenal medulla, and 20% for bovine adrenal cortex. PC 12 cells also contained predominantly MAO-A (90%); however, an increased Km for phenylethylamine and a sensitivity of deamination of this MAO-B substrate to inhibition by clorgyline are indicators of abnormal behavior of MAO in this clonal rat pheochromocytoma cell line.
 ...
PMID:Monoamine oxidase in rat and bovine endocrine tissues. 330 88

The effects of short- and long-term administration of a low dose of tranylcypromine on brain and urine levels of several biogenic amines and on brain activity of monoamine oxidases (MAO) A and B were investigated. MAO-A and MAO-B were inhibited by greater than 85% on day 1, and this inhibition continued to increase over the course of the study (42 days). Levels of 5-hydroxytryptamine in brain continued to increase up to day 21 and did not decline from day 21 to day 42, and levels of tranylcypromine itself continued to increase up to day 42. Dopamine concentrations peaked at day 10 and were not significantly different from that value by day 42. Brain levels of tryptamine and beta-phenylethylamine showed dramatic elevations after the first dose of the drug and remained essentially unchanged from those high values throughout the course of the drug treatment. Brain and urine increases in tryptamine and beta-phenylethylamine showed similar patterns, whereas urinary 5-hydroxytryptamine excretion reached maximal levels earlier than did brain levels.
 ...
PMID:Neurochemical changes in rat brain amines after short- and long-term inhibition of monoamine oxidase by a low dose of tranylcypromine. 333 60

In rodents, SR 95191 [3-(2-morpholinoethylamino)-4-cyano-6-phenylpyridazine] has been shown to be active in animal models of depression. The profile of activity of SR 95191 suggests that the compound is a selective and short-acting type A monoamine oxidase (MAO) inhibitor (MAOI) in vivo. In the present study, the interaction of SR 95191 with MAO-A and MAO-B activity was further examined in vivo and in vitro. In brain, liver, and duodenum of pretreated rats, SR 95191 selectively inhibited MAO-A (ED50 = 3-5 mg/kg, p.o.), whereas MAO-B was only weakly inhibited for doses as high as 300 mg/kg, p.o. In vivo, SR 95191 (1-100 mg/kg, p.o.) antagonized, in a dose-dependent fashion, the irreversible inhibition of brain and liver MAO-A induced by phenelzine. Finally, dopamine and 5-hydroxytryptamine depleted from their striatal stores by tetrabenazine were able to displace SR 95191 from the active site of MAO-A. However, ex vivo, kinetic studies showed that the inhibitory effect of SR 95191 (1-10 mg/kg) towards MAO-A was noncompetitive and was unchanged after dilution or dialysis. In vitro, the inhibition of brain MAO-A, but not MAO-B, by SR 95191 was time dependent, with a 19-fold decrease in the IC50 values being observed over a 30-min incubation period (140 to 7.5 microM). At this time, the SR 95191-induced inhibition of MAO-A was not removed by repeated washings. When the reaction was started by adding the homogenate without prior preincubation with SR 95191, the inhibition of brain MAO-A was fully competitive (Ki = 68 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Monoamine oxidase-inhibiting properties of SR 95191, a new pyridazine derivative, in the rat: evidence for selective and reversible inhibition of monoamine oxidase type A in vivo but not in vitro. 334 72

After i.p. injection of 30 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) daily for 4 days and sacrificing the rats 4 h after the last injection, striatal monoamine oxidase (MAO)-A and -B activities, assayed by conventional method with 5-hydroxytryptamine (5-HT) and benzylamine, were not changed. By an uptake technique, with dopamine as the substrate for both uptake and MAO, intrasynaptosomal MAO-A and -B activities were found to be greatly reduced with a greater MAO-A reduction. Intrasynaptosomal 5-HT oxidation by MAO-A was not changed in other forebrain regions treated with these MPTP doses. Similar results were also found with two brain preparations treated with single MPTP doses (30 mg/kg). This reduction in intrasynaptosomal MAO activity was completely absent after treatment with lower MPTP doses (15 mg/kg, daily for 5 days) and 5 days of a withdrawal period. The decrease in MAO activity might have been due to the decrease in DA transport into striatal synaptosomes during the enzyme assay and/or to reversible inhibition of intrasynaptosomal MAO by MPP+.
 ...
PMID:The ex vivo effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on rat intra- and extraneuronal monoamine oxidase activity. 349 Jun 38

The effect of the local anesthetics, tetracaine and bupivacaine, on monoamine oxidase (MAO) activity of rat brain and on the major steps of catecholamine and 5-hydroxytryptamine (5-HT) turnover was examined. The IC50 of tetracaine for MAO-A and MAO-B inhibition was 1.2 microM and 19.5 microM, respectively. Up to 2.5 mM bupivacaine was without effect on either form of MAO. None of the following activities in rat brain or adrenal medulla were inhibited by 5-2500 microM of tetracaine or bupivacaine: catecholamine-O-methyltransferase, tyrosine hydroxylase, dopamine-beta-hydroxylase. Tetracaine caused only a moderately potent inhibition of synaptosomal uptake of norepinephrine (NE) (IC50 14 microM), dopamine (IC50 37 microM) and 5-HT (IC50 45 microM). The potent and specific MAO inhibition by tetracaine, in association with an impaired uptake of synaptosomal amines, may lead to an increase in the synaptosomal content of neurotransmitter amines, such as 5-HT and NE, with possible antinociceptive consequences.
 ...
PMID:Differential effect of tetracaine and bupivacaine on catecholamine and 5-hydroxytryptamine turnover. 361 61

A coupled peroxidation technique for localization of monoamine oxidase (MAO-A and MAO-B), applied to post-mortem fixed tissue of the locus coeruleus of the Mongolian gerbil is demonstrated. Tyramine hydrochloride, beta-phenylethylamine and 5-hydroxytryptamine creatinine sulphate were used as substrates, 1-deprenyl and clorgyline served as specific inhibitors. All three substrates stained the neurons of locus coeruleus in the absence of inhibitor. In the presence of 1-deprenyl, tyramine hydrochloride and 5-hydroxytryptamine creatinine sulphate were metabolized, whereas in the presence of clorgyline no reaction with either substrate could be observed. Immunocytochemical staining of tyrosine hydroxylase (TH) was employed as comparison.
 ...
PMID:Histochemistry of MAO-A and MAO-B in the locus coeruleus of the Mongolian gerbil. 368 Dec 91

The inhibition of the A and B forms of monoamine oxidase (MAO) inside and outside serotonergic, noradrenergic, and dopaminergic synaptosomes in homogenates of rat hypothalamus or striatum by clorgyline, a selective and irreversible MAO-A inhibitor, and selegiline, a selective and irreversible MAO-B inhibitor, was examined. Intrasynaptosomal deamination at low concentrations of the substrates [14C]5-hydroxytryptamine ([14C]5-HT; 0.1 microM), [14C]noradrenaline (0.25 microM), [14C]3,4-dihydroxyphenylethylamine ([14C]dopamine; 0.25 microM), and [14C]tyramine (0.25 microM) was hindered by selective uptake inhibitors (citalopram, maprotiline, and amfonelic acid) in the incubation media. Thus, the difference between the deamination of 14C-amine in the absence and presence of the appropriate selective uptake inhibitor provided a measure of deamination in the specific aminergic synaptosomes. This was verified by determining the loss of MAO activity within noradrenergic and serotonergic systems after degeneration of the nerve terminals by the neurotoxins N-chloroethyl-N-ethyl-2-bromobenzylamine and p-chloroamphetamine. Results with the two inhibitors revealed that the A and B forms were responsible for 80 and 20%, respectively, of the deamination of [14C]5-HT within serotonergic synaptosomes from the hypothalamus. The deamination of [14C]noradrenaline within the noradrenergic synaptosomes from the hypothalamus and that of [14C]dopamine and [14C]tyramine within the striatal dopaminergic synaptosomes were due to MAO-A. About 10% of the deamination of [14C]noradrenaline, [14C]dopamine, and [14C]tyramine outside the noradrenergic or dopaminergic synaptosomes was brought about by the B form, with the remainder being deaminated by MAO-A.
 ...
PMID:A and B forms of monoamine oxidase within the monoaminergic neurons of the rat brain. 373 95


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>