Presence Of Monoamine Oxidase Research Articles

Aldose reductase: An aldehyde scavenging enzyme in the intraneuronal metabolism of norepinephrine in human sympathetic ganglia

The neurotransmitter norepinephrine is metabolized by monoamine oxidase into an aldehyde intermediate that is further metabolized to the stable glycol derivative, 3,4-dihydroxyphenylglycol (DHPG). In this study, the possible role of aldose reductase in reducing this aldehyde intermediate in human sympathetic neurons has been examined. DHPG is formed when norepinephrine is incubated with aldose reductase in the presence of monoamine oxidase. DHPG metabolism is inhibited by the monoamine oxidase inhibitor, pargyline which prevents the deamination of norepinephrine, and by the aldose reductase inhibitor AL 1576, which inhibits DHPG formation without affecting the deamination of norepinephrine. Although similar formation of DHPG was observed with human liver aldehyde reductase, the production of DHPG was more effective with aldose reductase than aldehyde reductase. Two peaks of reductase activity corresponding to aldose reductase and aldehyde reductase were observed when sympathetic ganglia were chromatofocused. Molecular modeling studies indicate that the energy-minimized structure of 3,4-dihydroxymandelaldehyde bound to aldose reductase is similar to that of glyceraldehyde where the 2′-hydroxyl group forms hydrogen bonds with Trp111 and NADPH. These results suggest that aldose reductase may be important in metabolizing the potentially toxic aldehyde intermediate formed from norepinephrine in human sympathetic ganglia.

Aldose reductase, a key enzyme in the oxidative deamination of norepinephrine in rats

The sympathoneural neurotransmitter norepinephrine (NE) is deaminated to 3,4-dihydroxymandelaldehyde (DHMAL) and subsequently converted to either 3,4-dihydroxymandelic acid (DHMA) or 3,4-dihydroxyphenylglycol (DHPG). In this study, we investigated the relative importance of aldose reductase versus aldehyde reductase in the formation of DHPG from DHMAL. The in vitro incubation of NE with aldose reductase in the presence of monoamine oxidase (MAO) resulted in the formation of DHPG, which was confirmed by mass spectrometry. Although aldehyde reductase also generated DHPG, its activity was much lower than that of aldose reductase. With northern blotting, the expression of both aldose reductase and aldehyde reductase was detected in rat superior cervical ganglia. However, with western blotting, only aldose reductase was immunologically detectable. Treatment of rats with aldose reductase inhibitors for 3 days increased the plasma level of DHMA. There was no correlation between the selectivity of inhibitors and effects on NE metabolite levels. A significant decrease in DHPG, however, was obtained only with an extremely high dose (9 mg/kg/day) of the nonselective inhibitor AL 1576. The present study confirmed that aldose reductase generates DHPG from NE in the presence of MAO. In rat sympathetic neurons, aldose reductase appears to be more important than aldehyde reductase for the formation of DHPG. However, when aldose reductase is inhibited, it appears that aldehyde reductase can compensate for the conversion of DHMAL to DHPG, indicating redundancy in the reduction pathway.

The effect of the monoamine oxidase inhibitor isocarboxazid on the canine metabolism of the cell-differentiating agent hexamethylene bisacetamide

The acute toxicities of the cellular differentiating agent hexamethylene bisacetamide (HMBA) in humans and animals include CNS toxicity (agitation, somnolence, seizures, hallucinations) and an anion-gap metabolic acidosis. N-Acetyl-1,6-diaminohexane (NADAH), the first metabolite of HMBA, is as active as the parent compound in causing differentiation of leukemic cells in vitro, whereas 6-acetamidohexanoic acid (6AcHA), which is formed by the oxidation of NADAH in the presence of monoamine oxidase (MAO) and aldehyde dehydrogenase, is inactive. To test whether the inhibition of MAO blocks the production of an inactive and possibly toxic HMBA metabolite (6AcHA) or increases the amount of active compounds (HMBA + NADAH) in vivo, we investigated the effect of the MAO inhibitor isocarboxazid on the metabolism and toxicity of HMBA in beagle dogs. Two groups of dogs, composed of one male and one female dog per group, were used in the study. One group received isocarboxazid (3.3 mg/kg p.o. q8h x 9) beginning at 24 h before the initiation of a 48-h i.v. infusion of HMBA (40 mg kg-1 h-1), whereas the other received placebo in an identical fashion prior to the start of an identical HMBA infusion. The mean plasma steady-state concentration (css) of HMBA was 0.91 mM in dogs given HMBA and isocarboxazid as opposed to 0.78 mM in those given HMBA and placebo. As measured spectrophotometrically, plasma MAO activity was inhibited by 86% +/- 3% in dogs receiving isocarboxazid. Gas chromatography/mass spectrometry detected 6AcHA in the plasma of animals that were given placebo but not in the plasma of dogs that received isocarboxazid. Gas chromatographic analysis of urine samples revealed that the total amount of 6AcHA and of NADAH excreted in urine was 8 times less and 3 times greater, respectively, in isocarboxazid-treated dogs than in animals that received HMBA and placebo. One dog was excitable after the initial two doses of isocarboxazid and developed seizures at the end of the HMBA infusion. Another dog was agitated during treatment with HMBA and isocarboxazid. No CNS toxicity occurred in animals that were treated with HMBA and placebo. We conclude that isocarboxazid inhibits the production of 6AcHA in vivo, thus supporting the involvement of MAO in HMBA metabolism. Because the combination of HMBA and isocarboxazid produces CNS toxicity, 6AcHA is probably not the neurotoxic agent in dogs.

Evidence for the presence of two types of monoamine oxidase in rabbit choroid plexus and their role in breakdown of amines influencing cerebrospinal fluid formation.

Abstract: The presence of monoamine oxidase (MAO) in the choroid plexuses from all brain ventricles of rabbit was established radiornetrically. Histochemical staining of MAO revealed the enzyme to be present primarily in the secretory epithelium. The mode of inhibition by the selective inhibitors clorgyline and deprenyl showed that type A and B MAO are present in approximately equal proportions in the plexus, Intraventricular administration of nialamide markedly reduced CSF production measured by [14C]inulin dilution during ventriculocisternal perfusion. The nialamide effect was significantly diminished after sympathetic denervation of the plexus, indicating that neuronal MAO is also present in the plexus; it probably represents a small fraction of the total MAO A activity in the tissue. In addition, nialamide tended to potentiate the reduction in CSF formation obtained by intraventricular noradrenaline.

Histochemical detection of monoamine oxidase activity in smooth muscle and epithelial tissues of Mytilus edulis L. and Mytilus galloprovincialisLMK.

Monoamine oxidase (MAO) activity was detected in the glio-interstitial tissue of the anterior byssus retractor muscle (ABRM) of Mytilus by the use of either dopamine or 5-HT as substrate and nitro blue tetrazolium salt as an electron receptor. Both substrates gave superimposable patterns. However, dopamine reactivity was very weak. Discrete but clear MAO activity was detected in the periphery of the smooth muscle cell, i.e., at the level of the peripherally localized mitochondria. The presence of MAO in the epithelium of the buccal palps was also demonstrated. These histochemical observations can be correlated with certain ultrastructural aspects, in particular the presence electron dense organelles profiles in glio-interstitial cells. This MAO activity is discussed in relationship with the high 5-HT content of ABRM and the control of its relaxation. Pigment formation and/or collagen tanning are discussed in terms of a possible relationship with inactivation of biogenic amines. These results complement previous data concerning the glio-interstitial tissue found in close association with muscle and nerve structures.

Characterization of rat skeletal muscle monoamine oxidase

Optimal conditions for deamination of 5-hydroxytryptamine in rat skeletal muscle were determined. The presence of monoamine oxidase (MAO) A and MAO B isozymes was demonstrated by the use of tyramine (a substrate of both forms), specific substrates (serotonin and benzylamine), and specific inhibitors (clorgyline and deprenyl) of MAO A and B respectively. A 6.5:3.5 ratio of MAO A to B was found using a whole muscle homogenate, while a 7.5:2.5 ratio was found with isolated mitochondria. Thermal inactivation studies demonstrated that skeletal muscle MAO A is more susceptible to heat inactivation than MAO B. The approximate proportion of muscle homogenate MAO which is present in sympathetic nerves was found to be 18 per cent, as determined by treating rats with 6-hydroxydopamine and quantifying the decrease in activity. Significant inhibition of MAO activity was observed after administration in vivo of the MAO inhibitors pargyline, tranylcypromine and harmaline.

Monoamine oxidase localization in the ependyma and infundibular recess in the catfish Clarias batrachus and its probable significance.

The presence of monoamine oxidase (MAO) in the cerebrospinal fluid (CSF) and MAO positive tracts bridging the CSF and the subependyma strongly suggest the involvement of CSF in the neuroendocrine control of hypophysial function.

Ultrastructural cytochemistry of p-N,N-dimethylamino-beta-phenethylamine (DAPA) oxidation reactions. "activation" and inhibition studies.

The oxidation of p-N,N-dimethylamino-beta-phenethylamine (DAPA) by amine oxidase(s) (AO), i.e., diamine oxidase (DAO), monoamine oxidase (MAO) and/or possibly other oxidases, has been previously demonstrated. This study reports the results of variations in fixation procedures and the incorporation of a series of possible "activators" and inhibitors into the DAPA oxidase (DAPAO) and DAPAO-BSPT [2-(2'-benzothiazolyl)-5-styryl-3-(4'-phthalhydrazidyl) tetrazolium chloride] reaction media in an attempt to elucidate the oxidase(s) involved. Results of these studies are indicative of at least two different oxidases acting preferentially on one or the other of the two systems. The presence of MAO, especially in unfixed tissue, and DAO, especially in fixed tissue, is denoted and that of other oxidase(s) is connoted.

Histochemical study of monoamine oxidase latency in the liver of the rat.

In a histochemical test system with adrenaline as substrate and nitroblue tetrazolium (NBT) as electron acceptor, an increase of NBT reduction in rat liver sections was found microspectrophotometrically following short hypotonic treatment. Investigations with iproniazide, a monoamine oxidase inhibitor, and non-enzymatic NBT reduction showed that the increased formazan formation was related to the presence of monoamine oxidase. It is suggested that the reason for the observed increase of formazan formation is due to increased permeability of the inner mitochondrial membrane to NBT. Consequently, the increase of monoamine oxidase observed in the histochemical test system does not represent mobilization of a latent activity, but rather complete assessment of activity that is normally present.

Transmural and subcellular localization of monoamine oxidase and catechol- O-methyl transferase in rabbit aorta

A quantitative study of monoamine oxidase (MAO) and catechol- O-methyl transferase (COMT) has been made on homogenates of adult rabbit thoracic aorta. Most of the activity of both enzymes is located in the tunica media. The ratio of adventitia/media distribution of COMT is considerably less than the corresponding ratio for MAO. The specific activities of MAO and COMT change in parallel through the greater part of the transmural profile obtained on 24 μ cryostat sections. The specific activity of COMT drops significantly in sections that include endothelium and subendothelial media, where no decrease in MAO is noted. Subcellular distribution studies indicate the presence of MAO in mitochondrial and microsomal fractions, compared to the predominantly microsomal and cell sap localization of COMT.

Evidence for the presence of monoamine oxidase in sympathetic nerve endings

Evidence for the presence of monoamine oxidase in sympathetic nerve endings