Multiple Forms Of Monoamine Oxidase Research Articles

Different roles for type A and type B monoamine oxidase in regulating synaptic dopamine at D-1 and D-2 receptors associated with adenosine-3',5'-cyclic monophosphate (cyclic AMP) formation.

The roles of multiple forms of monoamine oxidase (MAO) in regulating the synaptic concentration of dopamine, in the vicinity of dopamine receptors associated with cyclic AMP formation, was examined in striatal slices of the rat. d-Amphetamine (0.1 mumol/l to 20 mumol/l) caused a concentration-related increase in cyclic AMP formation, which correlated (in superfusion experiments) with the release of endogenously-formed dopamine. In the presence of (-)sulpiride (50 mumol/l), cyclic AMP formation was significantly increased at every concentration of d-amphetamine tested. At the same time, this concentration of (-)sulpiride had no effect on DA release. Inhibition of type A MAO with clorgyline (0.1 mumol/l) significantly enhanced the increase in cyclic AMP formation seen after d-amphetamine. By contrast, inhibition of type B MAO with deprenyl (0.1 mumol/l) was without effect on this action of d-amphetamine. At high concentrations of d-amphetamine (20 mumol/l), however, deprenyl + clorgyline treatment enhanced cyclic AMP formation to a greater extent than with clorgyline alone. Similar results could be obtained at lower concentrations of d-amphetamine (5 mumol/l), but only after inhibition of the dopamine neuronal reuptake system with nomifensine (30 mumol/l). Furthermore, in the presence of nomifensine, deprenyl alone was also able to significantly increase the cyclic AMP formation seen after d-amphetamine (5 mumol/l). In the presence of (-)sulpiride, relatively similar results were obtained following all MAO inhibitor treatments. These findings support the notion that type A MAO plays the primary role in regulating dopamine concentrations at D-1 and D-2 receptors within synapses of rat striatal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of maternal methadone administration on the development of multiple forms of monoamine oxidase in rat brain and liver

The development of total monoamine oxidase (MAO) and MAO-A and MAO-B in the forebrain, brainstem, cerebellum and liver of methadone-treated and normal rats were monitored with tryptamine, serotonin and benzylamine, respectively. Daily administration of methadone (10 mg/kg, s.c.) to pregnant and nursing rats substantially retarded the development of total and the A-form of MAO in the brain regions of pups but had no effect on that of MAO-B. The effect of methadone on the development of total MAO and MAO-A in the liver was only transient and less significant. This finding indicates that the perinatal opiate syndrome associated with maternal exposure to methadone is caused by the inhibition in MAO-A development in monoaminergic neurons in the brain.

Isoelectric focusing of isoenzymes of monkey brain monoamine oxidase

The multiple forms of monoamine oxidase (MAO) in monkey brain were investigated using an electrofocusing technique. When β-phenylethylamine (β-PEA) was used as substrate, two peaks (peak I and peak II) could be clearly distinguished from the profile; the isoelectric point (pI) values were near 7.8 and 6.3, respectively. When serotonin (5-HT) was used, MAO activity was observed in peak I enzyme. The peak I enzyme with a pI value of 7.8 contains AB-form MAO and oxidizes 5-HT and β-PEA, while peak II enzyme with a pI value of 6.3 contains B-form MAO and oxidizes β-PEA, respectively. However, when peak II enzyme was incubated in a pH 8.8 reaction medium, MAO activity toward 5-HT in peak II enzyme was seen.

Selective effects on catalysis by the multiple forms of monoamine oxidase produced by interactions of acidic phospholipids with mitochondrial membranes.

The effect of acidic phospholipids on the A and B multiple forms of membrane-bound mitochondrial monoamine oxidase has been investigated by incubating liposomes with isolated rat liver mitochondrial outer membrane preparations at lipid:protein ratios of 0.01 to 1. A strong inhibition of monoamine oxidase B was observed with phosphatidylserine and a moderate activation of monoamine oxidase A with phosphatidylinositol, while cardiolipin had no significant effect on either form. The specificity of phosphatidylserine inhibition for monoamine oxidase B was also confirmed in mitochondrial outer membrane isolated from tissues containing exclusively the A or B form of the enzyme (human placenta and bovine liver). Levels of incorporation were comparable for all the phospholipids and tissues studied and could not account for the different effects observed. Inhibition of monoamine oxidase B was found to be similar in an intact mitochondria preparation to that observed in the isolated outer membrane. A recent report of activation of both monoamine oxidase forms in delipidated whole mitochondria by the acidic phospholipids was re-examined and found to involve release of monoamine oxidase from the mitochondria. The details of the effects of phosphatidylserine and phosphatidylinositol on membrane-bound monoamine oxidase are consistent with the concept of the multiple forms as two distinct peptides, and suggest a second possible mode of in vivo regulation of substrate specificity.

Role of type A and type B monoamine oxidase in the metabolism of released [ 3H]dopamine from rat striatal slices

The effects of selective inhibition of multiple forms of monoamine oxidase (MAO) on the in vitro release and metabolism of newly-synthesized [ 3H]dopamine (DA) were examined using rat brain slices. Striatal slices were preincubated in the presence of [ 3H] l-tyrosine (20 μM) followed by a short incubation period in the presence of the selective irreversible MAO-inhibitor agents clorgyline (type A) and deprenyl (type B). Tissue pretreated in this manner was then subjected to a release incubation, and DA release and metabolism were determined under spontaneous and depolarizing conditions. Pretreatment with clorgyline (10 −7 M) significantly reduced the spontaneous, as well as K +-evoked, formation of both 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). Deprenyl (10 −7 M) pretreatment did not significantly affect these variables, but clorgyline + deprenyl pretreatment resulted in a reduction of both DOPAC and HVA that was greater than that produced by clorgyline alone. By contrast, deprenyl pretreatment significantly decreased both DOPAC and HVA under depolarizing conditions, but only in the presence of the DA uptake inhibitor nomifensine (10 −5 M). In the absence of MAO inhibition, nomifensine increased K +-evoked formation of DOPAC and HVA, while spontaneous formation was not affected. The results suggest that released DA is deaminated primarily by the type A form of MAO; however, in the absence of the type A MAO, or under conditions that promote exclusive postsynaptic deamination, minor but significant metabolism occurs via the type B enzyme. Data obtained are further discussed in relation to the mechanism of MAO-inhibitor drug action and pre- versus postsynaptic formation of DOPAC and HVA.

Effects of thyroidectomy on monoamine oxidase activities toward tyramine and serotonin in the circumventricular nuclei of the rat

Following thyroidectomy, monoamine oxidase (MAO) activities toward tyramine decreased significantly by 20% in the nucleus periventricularis and the nucleus arcuatus among the 3 hypothalamic nuclei of the rat, while MAO activity toward serotonin decreased significantly by 10% only in the nucleus periventricularis. It is suggested that thyroidectomy induced selective changes on the multiple forms of MAO in the discrete circumventricular nuclei.

Multiple forms of monoamine oxidase in human brain tumors

The multiplicity of monoamine oxidase (MAO) in human brain tumors was studied with a criterion of inhibitor sensitivity. All of the human brain tumors of glial origin, irrespective of their malignances, showed similar or lower ratios of type A MAO to type B MAO as compared with the normal cerebral hemispheres. This result is quite different from those of mouse neuroblastoma and rat glioma.

Subcellular localization of monoamine oxidase in bovine thalamus tissue using immunoferritin conjugates.

A combination of discontinuous sucrose gradient analysis and polyacrylamide electrophoresis was used to isolate one of the multiple forms of monoamine oxidase (MAO) from bovine thalamus. This substance (the principle form and the most anodic of the five MAO forms observed) was used as a basis for an immunoferritin-electron microscope approach to determine the subcellular localization of MAO in thalamus. This form of MAO, as well as antigenically related forms, was found to reside mainly on the outer mitochondrial membrane. In addition, the action of SDS on solubilization and interconversion of MAO forms was studied and found to be dependent on the concentration and time of reaction of SDS with thalamus tissue.

Multiple forms of monoamine oxidase and their interaction with tricyclic psychomimetic drugs

Multiple forms of monoamine oxidase and their interaction with tricyclic psychomimetic drugs

Inhibition by clorgyline and deprenyl of the different forms of monoamine oxidase in rat liver mitochondria

The type of inhibition of the different forms of monoamine oxidase by clorgyline (preferentially ‘A’ form-inhibiting) and deprenyl (preferentially ‘B’ form-inhibiting) has been investigated. For both inhibitors a reversible phase of inhibition was found to precede the irreversible reaction. When incubated at 25° for 20 min, clorgyline inhibited the ‘A’ form in an irreversible fashion, while 4 hr at 37° was needed to inhibit the ‘B’ form irreversibly. In contrast, deprenyl inhibited the ‘A’ form reversibly even when incubated at 37° for 4 hr, whereas the ‘B’ form was irreversibly inhibited under these conditions. The selectivity of both inhibitors was considerably lower with longer incubation times. The implications of the results for the interpretation of previous findings on multiple forms of monoamine oxidase (an ‘A’ and a ‘B’ form) and for chronic treatment with the inhibitors in vivo is discussed.

Multiple forms of monoamine oxidase: Fact and artefact

Multiple forms of monoamine oxidase: Fact and artefact

Multiple forms of monoamine oxidase in rabbit platelets

Rabbit platelets were found to contain both types A and B MAO activities. The specific enzymatic activity of rabbit platelet MAO was higher for the substrate serotonin than for phenylethylamine. The K m's for rabbit platelet MAO indicated that the MAO-B enzyme was similar to human platelet MAO and that both MAO-A and MAO-B enzymes in the rabbit platelet are similar to the corresponding forms in the rabbit brain. The drugs clorgyline and deprenyl confirmed the existence of types A and B MAO in the platelet and furthermore indicated that the type A form accounted for approximately 90% of the total enzymatic activity. Amitriptyline at low (micromolar) concentrations selectively inhibited MAO-B activity in both rabbit platelets and brain.

Ontogeny of multiple forms of monoamine oxidase in mouse brain

MAO activities in mouse brain responsible for deamination of serotonin (5-HT) and p-dimethylaminobenzylamine (DAB) were found to follow different postnatal developmental patterns. MAO activity which deaminated 5-HT reached adult levels 15 days after birth. At this age the capacity of brain to deaminate DAB was only 50% of adult levels and did not develop fully until after the 45th postnatal day. Inhibitor studies with Deprenil and clorgyline indicated that the deamination of the two substrates was due to different forms of MAO and that these forms were similar to type A and type B MAO described previously in rat brain.

Multiple forms of monoamine oxidase in human plasma

The presence of multiple forms of monoamine oxidase (MAO) in mitochondria has been suggested by many workers. Support for this hypothesis comes from kinetic studies including effects of selective inhibitors, substrate specificity, and thermal inactivation (1–7), and separation studies by chromatography or gel electrophoresis (8–13). Recently, McCauley and Racker (14) have demonstrated the separation of two immunologically distinct forms of the mitochondrial enzyme from bovine brain. However, the question of the true multiplicity of mitochondrial MAO remains unsettled due to controversies over methods of solubilization of the enzyme. To date, there has been little reported on possible multiplicity of soluble plasma MAO. Our recent investigation on human plasma MAO (15) has shown that MAO from a patient with hepatic fibrosis and hemochromatosis has different kinetic properties than the enzyme isolated from pooled normal human plasma. This finding suggested the possibility that human plasma may contain isoenzymes of MAO. In this communication, we report that three forms of MAO have been isolated in human plasma by hydroxyapatite column chromatography, and discuss some of their physical chemical properties.

Biogenic Amine-Containing Neurons: Biochemical Mechanisms of Synaptic Transmission

Brain contains multiple forms of monoamine oxidase. These enzymes are differentially effected by drugs and they appear to have preferred substrates. In the caudate nucleus, adenylate cyclase may be a receptor for dopamine. The waste products of amine metabolism are eliminated from CSF by a transport system located in the choroid plexuses.

Soluble and membrane-bound pig liver mitochondrial monoamine oxidase: Thermostability, tryptic digestability and kinetic properties

It has previously been shown that pig liver monoamine oxidase (monoamine: O 2 oxidoreductase, EC 1.4.3.4) can be rendered soluble in buffer by extraction with methylethyl ketone. The soluble enzyme can be rebound to delipidated membranes in the presence of highly acidic phospholipids. A comparison of the thermostabilities of the enzyme bound to the mitochondria and the soluble form showed that the soluble enzyme was much more labile than the bound enzyme. Rebinding of the soluble enzyme to relipidated membranes partially restored the thermostability. The soluble enzyme was more sensitive to tryptic digestion than the enzyme bound to mitochondria. Rebinding of the soluble enzyme to replipidated membranes did not decrease its sensitivity to trypsin. The role of membrane components in stabilizing the enzyme molecule is discussed. The change in the rate of tyramine oxidation with temperature was the same for both forms of the enzyme. Harmaline was found to reversibly inhibit both bound and soluble enzyme to the same degree. This was true both with tyramine and serotonin as substrate. However, serotonin oxidation by either form of the enzyme was inhibited more than tyramine oxidation. Pargyline irreversibly inhibited tyramine and serotonin oxidation to the same degree, both with the bound and the soluble enzyme. The molecular activity of the enzyme did not change after liberation from the membrane. The possibility that there are multiple forms of monoamine oxidase in the pig liver is discussed in the light of these findings.

Multiple forms of monoamine oxidase. Comparison of in vitro and in vivo inhibition patterns

Multiple forms of monoamine oxidase. Comparison of in vitro and in vivo inhibition patterns

Biochemical studies on hepatic fibrosis (XII) Multiple forms of monoamine oxidase in serum, liver mitochondria and various connective tissues

Biochemical studies on hepatic fibrosis (XII) Multiple forms of monoamine oxidase in serum, liver mitochondria and various connective tissues

Multiple forms of monoamine oxidase in developing Xenopus.

Das Isoenzymmuster der Monoaminoxidase verandert sich wahrend der fruhen Entwicklung der Larven vonXenopus laevis. Die Anzahl elektrophoretischer Banden verkleinert sich wahrend der Entwicklung von vier auf eine.

OCCURRENCE AND PROPERTIES OF MONOAMINE OXIDASE IN ADRENERGIC NEURONS

Abstract—Monoamine oxidase activity of peripheral organs of various species has been examined after surgical, chemical and immunological sympathectomy to assess the proportion of enzyme activity in adrenergic neurons and in extraneuronal cells. Significant falls in monoamine oxidase activity of vas deferens, submaxillary gland, iris and spleen were seen after sympathetic denervation although not in heart, small intestine and kidney. It was suggested that a correlation exists between the extent of the fall in monoamine oxidase activity after sympathectomy and the density of sympathetic innervation of the control organ. Studies of monoamine oxidase activity in vas deferens after inhibition with clorgyline suggested multiple forms of monoamine oxidase. Differences in inhibitor sensitivity, substrate specificity and thermal inactivation of monoamine oxidase in normal and denervated vas deferens were found and it was suggested that differences exist in the properties of the neuronal and extraneuronal monoamine oxidase.