Monoamine oxidase A and B: A useful concept?

Fowler, Christopher J.; Callingham, B. A.; Mantle, Timothy J.; Tipton, Keith F.

doi:10.1016/0006-2952(78)90262-9

Cited by 241 publications

(37 citation statements)

References 32 publications

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“…It is well known that two types of MAO, A and B, can be distinguished, and it is generally consid ered that many substrates are more specifically ca tabolized by one or the other type of MAO (Fowler et al, 1978). Pig brain tissue MAO is usually con sidered to be of the B type (Tipton and Spires, 1968), but in pig vascular tissue (both endothelium and smooth muscle) both types of MAO have been described (Trevethick et al, 1981), as in rat brain microvessels (Lai and Spector, 1978).…”

Section: Discussionmentioning

confidence: 99%

Monoamine Oxidase Activity in the Cerebral Vasculature: Comparison between Fresh Microvessels from Different Structures and Cell Cultures Derived from Microvessels

Sercombe¹,

Lasbennes²,

Drouet

et al. 1984

J Cereb Blood Flow Metab

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Summary: Monoamine oxidase (MAO) activity was studied in various preparations of porcine brain micro vessels to explore further the role of this enzyme in the blood-brain barrier to catecholamines, No difference was noted (V m and Km) between microvessels isolated from three structures (caudate nucleus, thalamus, and ce rebral cortex) in which the responses to circulating cat echolamines in vivo are markedly different. Large and small microvessels from the caudate nucleus and the thal amus presented the same specific activity. Cell cultures obtained from small microvessels were rich in endothelial cells as identified by the presence of Factor VIII -relatedIn a recent paper (Lasbennes et aI., 1983), we showed that the level of monoamine oxidase (MAO; EC 1.4.3.4) activity in brain microvessels, as mea sured by V m (the maximum activity of the enzyme with respect to a given substrate), was high for both artificial and natural substrates, with a high Km (the concentration of substrate giving one-half V m) ' sug gesting that this enzyme could play an efficient part in blood-brain barrier (BBB) mechanisms. It is generally believed that the cerebrovascular MAO is situated to a great extent in the endothelium, since a characteristic green fluorescence is seen in the endothelium after L-3,4-dihydroxyphenylalanine (L-DOPA) injection in animals treated with a MAO inhibitor (Bertler et al., 1966; Hardebo et aI., 1979). However, in spite of the BBB, circulating cateAddress correspondence and reprint requests to Dr. Sercombe at INSERM U 182, 10 avenue de Verdun, 75010 Paris, France.Abbreviations used: BBB, Blood-brain barrier; BSA, bovine serum albumin; HEPES, N-2-hydroxyethyl piperazine-N'-2-eth anesulfonic acid; 6-k-PGF la , 6-keto-prostaglandin Fla; L-DOPA, L-3,4-dihydroxyphenylalanine; M 199, medium 199; MAO, monoamine oxidase; NA, noradrenaline; PBS, phosphate-buff ered salt solution; PGE2, prostaglandin E2. 415antigen. These preparations displayed an MAO activity about ninefold less than freshly isolated microvessels, al though their prostaglandin synthetase activity appeared normal. These results suggest that MAO activity is not the main factor determining the regional differences in the cerebrovascular reactions to catecholamines, that MAO is not specifically localized in the endothelium but must be also present in the smooth muscle, and that the MAO activity is greatly decreased during cell culture.

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Section: Discussionmentioning

confidence: 99%

Monoamine Oxidase Activity in the Cerebral Vasculature: Comparison between Fresh Microvessels from Different Structures and Cell Cultures Derived from Microvessels

Sercombe¹,

Lasbennes²,

Drouet

et al. 1984

J Cereb Blood Flow Metab

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“…Some examples of 'unusual' combinations towards three of the most commonly used substrates are shown in Table 2. It has been found, for both 5-HT and p-phenethylamine as substrate in a variety of tissues, that the substrate specificities of the two forms of MA0 are dependent upon the concentration of substrate used to assay for enzyme activity (Kinemuchi et al 1979;Ekstedt 1979;Dial & Clarke 1979;Suzuki et al 1979;Peers et al 1980;Sourkes 1980 (Roth 1976;Fowler et a1 1980a,b), human platelet (Winter et a1 1978;Fowler et a1 1979a;McEntire et a1 1979;, rat heart (Fowler & Callingham 1979) and rat liver (Fowler & Oreland 1980a,b).…”

Section: Substrate-specificity Of Monoamine Oxidasementioning

confidence: 99%

The acetylenic monoamine oxidase inhibitors clorgyline, deprenyl, pargyline and J-508: their properties and applications

Fowler

Oreland

Callingham

1981

Journal of Pharmacy and Pharmacology

101

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The article presents a short review of some of the properties of the acetylenic inhibitors of monoamine oxidase currently under investigation: clorgyline, (-)-deprenyl, pargyline and 5-508. Their substrate-selective inactivation, mechanism of inhibition, titration and pharmacology with respect to monoamine oxidase are critically discussed.In 1968, Johnston showed that the irreversible acetylenic inhibitor clorgyline (N-methyl-N-propargyl-3-(2,4-dich1orophenoxy)-propylamine) inhibited the oxidative deamination of 5-hydroxytryptamine by rat brain monoamine oxidase (MAO, monoamine 0,: oxidoreductase (flavine containing), EC 1.4.3.4) at concentrations that were much lower than were required for the inhibition of benzylamine oxidation (Johnston 1968). When tyramine was used as substrate, a biphasic pattern of inhibition was found. Such a result has been found for a number of tissues, including the rat liver (Hall et al 1969, see Fig. I). Johnston (1968) suggested that these results were due to the presence of two forms of monoamine oxidase, which are now generally termed MAO-A and -B, where the -A form is sensitive to inhibition by clorgyline, and the -B form more resistant to inhibition. This conclusion was reinforced by the introduction of the MAO-B selective inhibitor (-)-deprenyl (phenyl-isopropy I-methyl-propinylamine) (Knoll & Magyar 1972) and its more potent analogue 5-508 (N-methyl-N-propargyl-(I-indany1)-ammonium hydrochloride) (Knoll et a1 1978). The structures of the compounds are given in Fig. 2. In addition, a variety of agents, ranging from the tricyclic noradrenaline uptake inhibitors to local anaesthetics, have been found to inhibit M A 0 activity in a substrate-selective manner (for review, see Fowler et a1 1978).In this article, the most commonly used substrateselective inhibitors, the acetylenic inhibitors of which clorgyline and (-)-deprenyl are the most well known, have been reviewed with respect to their properties, since it has been these compounds that have provided the main impetus for research in MA0 over the last decade. Substrate-specificity of monoamine oxidaseMost of the early studies with clorgyline and (-)-deprenyl were performed on either rat brain or liver, where it was shown that 5-hydroxytryptamine was the preferred substrate for MAO-A and benzylamine the preferred substrate for MAO-B, whilst tyramine was found to be deaminated by both enzyme forms (Johnston 1968; Hall et a1 1969). However, this substrate specificity is by no means universal. In Table I, the data published over the last ten years have been investigated in order to determine the frequency of occurrence of the metabolism of a given substrate by a given enzyme form. The 'common substrate' tyramine, for example, is in fact metabolized by both enzyme forms in only 29 out of 51 tissues (see Table I). Most of the possible combinations of the substrate specificities of the two forms of M A 0 have been reported. Some examples of 'unusual' combinations towards three of the most commonly used substrates are shown in Table 2...

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“…In vitro, it causes sucicide inhibition of MAO-B because it acts as a substrate for both forms, and the resulting product then forms a stable adduct with the active site of MAO-B, whereas with MAO-A, the role of MD 780236 as a substrate predominates (20)(21)(22). Benzylcyanide, which was also used in this study causes selective inhibition of MAO-B (14,15).…”

Section: Discussionmentioning

confidence: 99%

Enzymic and molecular characteristics of a new form of monoamine oxidase, distinct from form-A and form-B.

et al. 1984

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Monoamine oxidase A and B: A useful concept?

Cited by 241 publications

References 32 publications

Monoamine Oxidase Activity in the Cerebral Vasculature: Comparison between Fresh Microvessels from Different Structures and Cell Cultures Derived from Microvessels

Monoamine Oxidase Activity in the Cerebral Vasculature: Comparison between Fresh Microvessels from Different Structures and Cell Cultures Derived from Microvessels

The acetylenic monoamine oxidase inhibitors clorgyline, deprenyl, pargyline and J-508: their properties and applications

Enzymic and molecular characteristics of a new form of monoamine oxidase, distinct from form-A and form-B.

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