Properties of monoamine oxidase in mouse neuroblastoma N1E-115 cells

Monoamine oxidase (MAO) from adrenergic mouse neuroblastoma N1E-115 cells was compared to MAO found in rat and mouse brain, rat superior cervical ganglion, and human platelet. In comparison to MAO from brain and ganglion, mouse neuroblastoma MAO deaminated 5-hydroxytryptamine (5-HT) to a proportionately greater extent than all other substrates studied, with benzylamine deamination representing only 1 per cent that of 5-HT. Neuroblastoma MAO was over 1000 times more sensitive to inhibition by clorgyline than by deprenyl. With increasing concentrations of clorgyline, inhibition of tyramine deamination was represented by a simple sigmoid curve, suggesting the presence of primarily one form of MAO. Our results are consistent with evidence for a specific form of MAO associated with sympathetic neurons and suggest that neutoblastoma N1E-115 cells are highly enriched in MAO type A.     

Monoamine oxidase activity of macrophages at rest and during phagocytosis

Mouse macrophages contain monoamine oxidase (MAO) A activity and traces of MAO B, as judged by a strong deamination of 5-hydroxytryptamine and tyramine and a marginal one of benzylamine. Significant inhibition of MAO activity occurred in the presence of the specific inhibitors clorgyline and deprenyl. MAO A activity was considerably depressed in phagocytizing cells.     

Binding and deamination of various substrates by types A and B monoamine oxidase in bovine brain mitochondria

The binding and deamination of four substrates by type A and type B monoamine oxidase (MAO) in bovine brain mitochondria were investigated in mixed substrate experiments. MAO activity in bovine brain mitochondria, with 5-hydroxytryptamine (5-HT) as substrate, was highly sensitive to clorgyline and less sensitive to deprenyl, while MAO activity with benzylamine or β-phenylethylamine (PEA) as substrate was highly sensitive to deprenyl and less sensitive to clorgyline. On the other hand, when tyramine plus PEA was used as substrate, the inhibition curves of clorgyline and deprenyl were both biphasic. These results indicate that 5-HT and benzylamine were preferentially deaminated by type A MAO and type B MAO, respectively, and that tyramine and PEA were deaminated by both types of MAO. Studies on the inhibition by clorgyline plus deprenyl of tyramine deamination (in the absence and presence of another substrate) showed that the deamination of tyramine by both type A and type B MAO was inhibited by PEA or benzylamine, while only type A MAO was inhibited significantly by 5-HT. The KA_i value, the dissociation constant of the type A MAO and 5-HT complex, and the KB_i values, the dissociation constants of the type B MAO and PEA or benzylamine complex, were almost equal to the K_m values of type A MAO and type B MAO respectively. The KA_i values for PEA and benzylamine were 78 and 58 μM respectively. For the type B MAO-5-HT complex, the dissociation constant KB_i was 1447 μM. These results show that type A MAO deaminates tyramine and 5-HT whereas benzylamine is not deaminated, but only binds to the substrate binding site of type A MAO with almost the same rate as that for deamination by type B MAO; with type B MAO, tyramine, PEA and benzylamine are deaminated, whereas 5-HT is not deaminated and binds to the substrate binding site of type B MAO with low affinity.     

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.     

Distribution and inhibition characteristics of human brain monoamine oxidase.

Monoamine oxidase (MAO) activity in 14 regions of 10 normal post-mortem human brains using 5-hydroxytryptamine (5HT), benzylamine, tyramine and dopamine as substrates is presented. Regional distribution with 5HT, benzylamine and tyramine was generally similar with the highest activities observed in the hypothalamus. However, with dopamine as substrate, highest MAO activity occurred in the nucleus accumbens. Although there was relatively greater MAO activity towards 5HT than towards benzylamine in all four cerebral cortical areas studied compared with the caudate, putamen, accumbens and hypothalamus this apparently greater proportion of type A MAO in cortex could not be confirmed with the use of the specific inhibitor clorgyline. In some cases inhibition curves with clorgyline (and correspondingly with deprenyl) were not the expected double sigmoid shape. It is suggested that characterisation of MAO by techniques dependent on the use of specific inhibitors in samples of human brain collected and stored in the usual manner may prove difficult to interpret.     

Substrate specificity and inhibitor sensitivity of monoamine oxidase in rat kidney mitochondria.

The deamination of the substrates 5-hydroxytryptamine (5-HT), tyramine, dopamine, β-phenylethylamine and benzylamine by rat kidney mitochondrial monoamine oxidase (MAO) was studied, and kinetic constants are reported for each substrate. By the use of the selective MAO inhibitors, clorgyline and deprenyl, 5-HT and benzylamine were found to be substrates for types A and B MAO, respectively, in this tissue, whereas the other substrates were metabolized by both forms of MAO. No evidence for any significant metabolism of 5-HT or benzylamine by other amine oxidases was obtained. However, some conditions under which the carbonyl reagents semicarbazide, isoniazid and aminoguanidine may interfere with assays for MAO, without actually affecting enzyme activity directly, are described. Preincubation of kidney mitochondria with histamine resulted in a time- and oxygen-dependent irreversible inhibition of both type A and type B MAO activity; the exact nature of the inhibitory agent and its mode of action remain to be determined.     

Effect of nonselective and selective inhibitors of monoamine oxidases A and B on pethidine toxicity in mice.

The LD50 of pethidine was determined in mice pretreated (4 h) either with the nonselective monoamine oxidase (MAO) inhibitor, phenelzine or with clorgyline, a selective inhibitor of MAO A or deprenyl, a selective inhibitor of MAO B. Phenelzine or combined clorgyline plus deprenyl pretreatments decreased pethidine LD50. Clorgyline or deprenyl alone did not affect pethidine toxicity. Whole brain 5-hydroxytryptamine (5-HT) concentrations were measured in the pretreated mice. 5-HT levels were approximately doubled (P less than 0.001) after phenelzine or clorgyline plus deprenyl treatment, but not after clorgyline or deprenyl given alone. These results indicate that both MAO A and MAO B need to be inhibited to increase pethidine toxicity and brain 5-HT levels. They support the involvement of 5-HT in the toxic interaction between pethidine and MAO inhibitors.     

β-Phenylethylamine and benzylamine as substrates for human monoamine oxidase A: A source of some anomalies?

Monoamine oxidase (MAO) A predominates both in human placenta and lung. With 5-hydroxytryptamine (5-HT), β-phenylethylamine (PEA) and benzylamine (Bz) as substrates and clorgyline and deprenyl, respectively, as selective MAO A and B inhibitors, their activity pattern has been defined and compared with that of human liver. PEA had a much higher V_max with placental MAO A than did Bz; it behaved largely as an A substrate in placenta, and partly as an A substrate in lung. At commonly used substrate concentrations, deamination of Bz (sensitive to 10^?7 M deprenyl) was a better indicator of MAO B activity than deamination of PEA. The divergence between PEA and Bz as MAO A and B substrates may be one reason for some of the apparent discrepancies in the behaviour of MAO A and B noted in a variety of tissues in the literature.However, Bz reacts with benzylamine oxidase (BzAO) as well as MAO B. Depending on the tissue, deprenyl-resistant Bz activity may indicate the presence of BzAO rather than MAO A. As there is a widespread distribution of BzAO in man and rat, BzAO should be considered among the alternatives of enzyme activity when Bz is used as substrate.     

Cumulative effects of irreversible MAO inhibitors in vivo

The effects of repeated treatment with clorgyline, pargyline, deprenyl and tranylcypromine on MAO activity in rat brain and liver were investigated. MAO was measured with the substrates serotonin (5HT), phenethylamine (PEA) and, in some cases, t brain tissue after single and repeated administrations of 10 mg/kg s.c. clorgyline or deprenyl were also compared. Single doses of clorgyline (1 and 10 mg/kg s.c.) completely blocked the deamination of 5-HT. PEA deamination gradually decreased during the 14-day treatment. Pargyline in a dose of 0.3 mg/kg s.c. reduced both 5-HT and PEA deamination progressively over the same period. In the course of repeated treatment the effects of clorgyline and deprenyl on 5-HT and PEA deamination increased in intensity, by a factor of about 10 in the brain and about 3 in the liver. The potentiation of the effect of tranylcypromine was less marked (brain: × 4; liver: × 2). The rates of recovery of MAO activity were not greater after repeated than after single administrations of high doses of clorgyline and deprenyl, suggesting that the withdrawal of the drugs is not followed by a rebound phenomenon. Our results indicate that repeated treatment with suitable doses of clorgyline or deprenyl leads to specific reduction of either MAO A or B activity in brain, without producing any appreciable effect in the liver.     

Studies of monoamine oxidases: Inhibition of bovine brain MAO in intact mitochondria by selective inhibitors

The inhibition of mitochondrial monoamine oxidase (MAO) from beef brain cortex by the selective inhibitors, clorgyline, harmaline, Deprenyl and pargyline, was compared using five substrates: serotonin (5-HT), β-phenylethylamine (PEA), tyramine, tryptamine and dopamine. Dose-response studies, consistent with the classification of MAO, types A and B, indicated that serotonin deamination was more sensitive to clorgyline and harmaline inhibition than was phenylethylamine. However, the curves for all substrates were double-sigmoidal, rather than being a single sigmoid curve for 5-HT and PEA. Deprenyl and pargyline did not exhibit any marked selectivity for inhibiting PEA deamination without prior preincubation of enzyme and inhibitor. The rate of inhibition was variable and was dependent upon the substrate, the nature of the inhibitor and the inhibitor concentration. Dual inhibitor studies, using the “type A” inhibitor, clorgyline, and the “type B” inhibitor, Deprenyl, together, resulted in almost complete MAO inhibition, regardless of substrate. Combining the two type A inhibitors, clorgyline and harmaline, or the two type B inhibitors, deprenyl and pargyline, resulted in inhibitions that were equal to or only slightly greater than the inhibition produced by a single inhibitor. These results suggested that there are at least two distinct sites in beef brain MAO from cortical mitochondria which may be interacting. The deamination of all substrates occurs at both sites.     

Studies on the subcellular localization of monoamine oxidase types A and B and its importance for the deamination of dopamine in the rat brain

The distribution of the MAO-forms A and B between intra- and extrasynaptosomal rat brain mitochondria was studied with the aid of their known substrate and inhibitor specificities. The activities with the selective substrates serotonin, PEA and benzylamine indicated that intrasynaptosomal mitochondria have about a 3.4-fold higher MAO A:MAO B ratio than extrasynaptosomal mitochondria. However, PEA was found to be a selective substrate for MAO B only at low concentrations (such as 5 × 10^?6M), whereas at higher concentrations (such as 10^?3M) it was a substrate for both forms of MAO. The different ratios of the two enzyme forms in the two mitochondrial populations were confirmed when the selective inhibitors clorgyline and deprenyl were used with dopamine or 10^?3M PEA. With these two amines, the ratios of MAO A: MAO B activities were 3–4.5 times higher in intrasynaptosomal than in extrasynaptosomal mitochondria. In particular, when the activity with dopamine was measured in intact synaptosomes, deamination being preceded by a specific uptake into these particles, the inhibitor sensitivities clearly showed that MAO activity was almost exclusively attributable to the A-form of the enzyme. Thus, mitochondria in the terminals of dopaminergic neurones have an even more pronounced enrichment in MAO A than the mitochondria obtained by osmotic lysis of a total brain synaptosomal preparation. It was also found that clorgyline and deprenyl have an inhibitory effect on the uptake of dopamine into nerve endings with IC₅₀ values in the range of 10^?5 to 10^?4M. These results are discussed in terms of possible physiological significancies of the properties and distribution of the two forms of MAO.     

Serotonin oxidation by type B MAO of rat brain

The two MAO types in rat brain can be selectively inhibited by administering intraperitoneal injections of clorgyline or pargyline in suitable doses. Brain mitochondria prepared from such animals exhibit type B or type A MAO activity, respectively. In vitro clorgyline and deprenyl dose-response curves confirmed the purity of the enzyme preparations. Specific activities and K_m values of such preparations were determined for tyramine, serotonin and benzylamine. Type B and type A MAO were found to oxidize serotonin and benzylamine. respectively, although they had low affinities. Serotonin oxidation by mitochondria prepared from clorgyline treated animals showed type B characteristics also in its heat inactivation time course.     

Monoamine oxidase in pancreatic islets,exocrine pancreas,and liver from rats. Characterization with clorgyline,deprenyl, pargyline,tranylcypromine, and amezinium

Monoamine oxidase (MAO) was characterized in tissue homogenates from pancreatic islets, exocrine pancreas, and liver from rats. Phenylethylamine was preferentially deaminated by pancreatic islet MAO while 5-hydroxytryptamine was preferentially deaminated by MAO from exocrine pancreas, and tyramine was a good substrate for both tissues. All three substrates were well deaminated by liver tissue. Clorgyline, a selective inhibitor of MAO-A, preferentially inhibited deamination of 5-hydroxytryptamine by all three tissue homogenates, while deprenyl, a selective inhibitor of MAO-B, preferentially inhibited deamination of phenylethylamine. In the case of pargyline, a less selective MAO-B inhibitor, the preference in favour of phenylethylamine was less pronounced. According to these results, MAO in pancreatic islets can be classified as predominantly type B enzyme species and MAO in exocrine pancreas as predominantly type A enzyme species while both types of the enzyme are present in the liver. Using the same three MAO substrates and compared with the effects of the selective enzyme inhibitors, clorgyline and deprenyl, tranylcypromine can be classified as a potent nonselective inhibitor of MAO in homogenates of all three tissues investigated with a slight preference in favour of the inhibition of the B-form of the enzyme, while in contrast amezinium can be classified as a weak nonselective inhibitor of MAO with a slight preference in favour of the inhibition of the A-form of the enzyme. All MAO inhibitors tested also inhibited insulin secretion by isolated incubated rat pancreatic islets, however only at IC50 which were two to three decimal powers higher than those necessary for the inhibition of the MAO activity, thus indicating that inhibition of MAO activity and inhibition of insulin secretion are apparently not closely related.     

Association of monoamine oxidase with lipid--a comparative study mitochondria from Novikoff hepatoma and rat liver.

Monoamine oxidase (MAO) from Novikoff hepatoma and liver of the rat host has been studied. MAO in the mitochondria from the fast growing hepatoma was determined to be predominantly of the A type by studies carried out with the irreversible inhibitors clorgyline and deprenyl. The enzyme from the host liver was similar to that reported for normal rat liver MAO. In order to investigate the role lipid may play in the genesis of different types of MAO, the hepatoma mitochondria were investigated as a model for type A MAO and compared to the host liver mitochondria which were shown to have both types of MAO activity. Phospholipid analysis of both hepatoma and host liver mitochondria revealed no significant difference in the proportion of outer membrane phospholipids. Delipidation with methyl ethyl ketone of both mitochondrial preparations resulted in the inactivation of type A MAO, which could be reactivated partially by mitochondrial lipids, but not by purified phosphatidylcholine. Low recovery of type B MAO after delipidation of the hepatoma mitochondria suggests that transformation of type A to type B MAO does not occur. Arrhenius plots of MAO activity revealed that type B MAO was sensitive to a phase transition of the outer mitochondrial membrane. The energy of activation of type B MAO as estimated by benzylamine deamination was reduced by 47 per cent at temperatures below 13°. Delipidation of mitochondria also resulted in a similar decrease in the energy of activation of type B MAO at all temperatures tested. Both types of MAO were shown to be labile to freeze/thawing as a result of delipidation. The results suggest that both types of MAO are integrally associated with the lipid environment of the outer mitochondrial membrane and that the association of lipid with the two types of MAO is different.     

N-propargylbenzylamine, a major metabolite of pargyline, is a potent inhibitor of monoamine oxidase type B in rats in vivo: a comparison with deprenyl.

In an effort to explore the contribution of the metabolites of pargyline towards the in vivo inhibition of monoamine oxidase (MAO), the effects of pargyline and its major metabolites on the production and metabolism of a number of biogenic amines were studied in rats. The administration of pargyline gave rise to three major ethyl acetate extractable metabolites: benzylamine, N-methylbenzylamine and N-propargylbenzylamine (NPB). Only NPB demonstrated in vivo monoamine oxidase inhibitory properties at an acute dose of 30 mg kg-1. The acute effects of pargyline, NPB, and deprenyl on urine and brain concentrations of a number of biogenic amines (phenylethylamine (PEA), m- and p-tyramine, noradrenaline (NA), dopamine, and 5-hydroxytryptamine (5-HT) and their metabolites were evaluated. Increased urine and brain concentrations of PEA were considered to represent in vivo inhibition of type B MAO while decreased concentrations of NA and 5-HT metabolites were regarded as indicators of an in vivo inhibition of MAO type A. NPB, like deprenyl and pargyline, significantly increased urine and brain PEA while only pargyline reduced 5-HT metabolism, suggesting that the metabolism of pargyline to NPB may contribute towards the MAO type B inhibitory effects of pargyline in vivo. Since the therapeutic benefits of MAO inhibitors in clinical practice usually require some period of chronic treatment, the chronic effects of repeated 14 daily doses of the above MAO inhibitors on central and peripheral biogenic amines were evaluated at the following times: during treatment, one day and five days after termination of treatment. The biochemical changes observed during the course of chronic NPB, pargyline and deprenyl treatments generally follow the expected in vitro characteristics of these drugs, but the detailed changes observed suggest clear differences. For example, the in vivo effect of pargyline on urine 5-hydroxyindoleacetic acid excretion was considerably weaker than its effect on the excretion of NA and dopamine metabolites. These changes are opposite to the in vitro effects of pargyline on 5-HT, dopamine and NA oxidative deamination. Inhibitions of the metabolism of all the amines studied were clearly observed during chronic MAOI treatments, but these effects were less evident five days after the end of treatment, suggesting an almost normal metabolism of biogenic amines. It is concluded that while MAO inhibitors may be the primary compound responsible for MAO inhibition, the effects of their metabolites in some cases may also play equally important roles in the regulation of monoamines both in the periphery and the brain.(ABSTRACT TRUNCATED AT 400 WORDS)     

Studies on beta-phenylethylamine deamination by human placental monoamine oxidase

Kinetical properties of human placental monoamine oxidase (MAO) were investigated in studies on inhibitors and mixed substrates. MAO activity was determined by a radioisotopic assay. Lineweaver-Burk plots were linear at higher and lower concentrations of PEA, whereas at intermediate substrate concentrations, a downward curving plot was obtained. The Km values of the low- and high-affinity sites for PEA deamination were estimated. Studies with mixed substrates showed that 5-HT was a competitive inhibitor and tyramine a mixed-type inhibitor of deamination at high concentrations of PEA, whereas both were non-competitive inhibitors at lower concentrations of PEA. After pre-incubation of human placental mitochondrial preparations with deprenyl, Lineweaver-Burk plots were completely linear, and the Km value was the same as that obtained at low concentrations of PEA in the absence of deprenyl. Tyramine and 5-HT were competitive inhibitors of PEA deamination by deprenyl-treated MAO. From these results it is concluded that there are two kinds of MAO with high- and low-affinity sites for PEA in mitochondria of human placenta, corresponding to type B and A Mao, and that tyramine, 5-HT and PEA share a substrate-binding site on type A Mao, while tyramine and 5-HT bind to a site on type B MAO that is different from the PEA binding site.     

In vivo, noradrenaline is a substrate for rat brain monoamine oxidase A and B

In vivo clorgyline (5 mg/kg) and (-)-deprenyl (5 mg/kg) selectively inhibit monoamine oxidase (MAO) type A and B activities in rat brain hypothalamus and caudate nucleus using 5-hydroxytryptamine (5-HT), noradrenaline (NA), and beta-phenylethylamine (PEA) as substrates. Clorgyline induces a significant increase in NA concentrations of hypothalamus and caudate nucleus; however (-)-deprenyl is without effect. The combination of clorgyline and (-)-deprenyl at the above doses completely inhibits both forms of MAO, resulting in an even greater increase in NA levels in both brain areas than observed with clorgyline. The non-selective inhibitor tranylcypromine (5 mg/kg) produced a similar effect. Rats pretreated with the selective or the non-selective inhibitors but given L-DOPA (50 mg/kg) have a similar pattern of brain NA, but its concentrations are higher in both brain regions. The results indicate that although in vitro NA may be an exclusive substrate for MAO type A, in vivo, when this enzyme form is selectively inhibited, NA at high concentrations can be a substrate for MAO type B.     

The isolated perfused rat brain preparation in the study of monoamine oxidase and benzylamine oxidase: Lack of selective brain perfusion

Monoamine oxidase (MAO) is present in brain blood vessels, and a different amine oxidase, benzylamine oxidase (BzAO), is claimed to exist in porcine cerebral vessels. The object of the present investigation was to evaluate these deaminating activities in the structurally intact brain, utilizing the isolated perfused rat brain preparation (IPRB). [¹⁴C]Benzylamine (10 μM), a substrate for both BzAO and MAO, was perfused via the internal carotid arteries for 5 min, and deaminated metabolites were measured. BzAO and MAO activities were distinguished by the use of the selective inhibitors semi-carbazide and pargyline. Both BzAO and MAO deaminated benzylamine (10 μm), but over 90 per cent of the total deaminated products resulted from BzAO. This was due to the much lower K_m, value of benzylamine for BzAO (2.8μM) than for MAO (169 μM). In vitro assays, however, revealed that the brain contained no measurable BzAO activity, whereas all other head structures (skull, mandible, skin, skeletal muscle, eyes, periocular tissues and tongue) contained BzAO activity. MAO was present both within and outside the brain. These results suggest that the IPRB preparation is not specific for brain perfusion. Experiments with technetium-labeled microspheres showed that, although the brain is preferentially perfused on a per gram basis, 52 per cent of the total perfusate passed through the skull and 13 per cent through extracranial structures. Only 35 per cent was specific for the brain. Other experiments showed that perfusion of the intact rat head produced greater deamination of benzylamine than when the skin and 70 per cent of the muscle were removed. Additionally, perfusion via the pterygopalatine arteries, to bypass the brain, resulted in increased deamination. It is concluded that the IPRB preparation is not specific for brain perfusion and that BzAO activity is present in all head structures other than the brain. The presence of BzAO in bone, skin, and muscle is consistent with suggestions for a physiological function of the enzyme in connective tissue.     

The effect of selective type A or type B monoamine oxidase inhibition on the intrasynaptosomal deamination of (3H)serotonin in rat spinal cord tissue

Summary The degree to which the type A and type B forms of monoamine oxidase participate in the intraneuronal deamination of (³H)serotonin (5-HT) was examined in synaptosomal-rich fractions of rat spinal cord tissue. Synaptosomes were labeled with (³H)5-HT and superfused with physiological buffers containing selective concentrations of a type A (clorgyline) or a type B (deprenyl) MAO inhibitor. The efflux of (³H)5-HT and newly-formed (³H)5-hydroxyindoleacetic acid (5-HIAA) was determined and compared to controls over time. In control samples, a slight decline in (³H)5-HT efflux occurred over the experimental superfusion period. However, a stable formation and efflux of (³H)5-HIAA was seen during this same period of time. When clorgyline was added to the superfusion buffer, a rapid decline in superfusate levels of (³H)5-HIAA was observed. Similar experiments in the presence of deprenyl were without effect. In order to elevate cytoplasmic concentrations of (³H)5-HT and therefore increase its chances for interaction with nerve terminal MAO, reserpine was added to the superfusion buffer. Reserpine caused a greater than 3-fold increase in (³H)5-HIAA formation with no change in (³H)5-HT efflux. Clorgyline inhibited this increase in (³H)5-HIAA formation but deprenyl was again without effect. In the presence of clorgyline, reserpine also caused an increase in (³H)5-HT efflux. These results strongly support the notion that 5-HT deamination within rat spinal cord nerve terminals occurs primarily, if not exclusively, through an interaction with type A MAO.Abbreviations 5-HT 5-hydroxytryptamine, serotonin - MAO monoamine oxidase - 5-HIAA 5-hydroxyindoleacetic acid Supported in part by N.I.H. grants GM 30002, 5-T32-GM 07039, and the West Virginia University Medical Corporation. L. M. B. was supported by a Swiger Fellowship     

MAO types in guinea pig liver mitochondria

MAO of guinea pig liver mitochondria actively deaminated dopamine, tyramine, serotonin and 5-methoxy-tryptamine, while tryptamine, 5-methyl-tryptamine and 7-methyl-tryptamine were moderately deaminated. Very little deamination occurred when benzylamine. noradrenaline and β-phenylethylamine were used as substrates. The in vitro inhibition patterns of MAO of guinea pig liver mitochondria by some selective inhibitors were investigated in the presence of tyramine, tryptamine and serotonin. Tryptamine oxidation showed biphasic inhibition pattern with harmaline, clorgyline and Lilly 51641, while the inhibition curves in the presence of pargyline and deprenyl were sigmoidal. The inhibition curves for tyramine oxidation were biphasic with all the inhibitors except pargyline. Serotonin-MAO inhibition curves, on the other hand, were sigmoidal with all the inhibitors except Lilly 51641. Thermal treatment of guinea pig liver mitochondria produced rapid inactivation of serotonin and tryptamine oxidizing activity, while benzylamine oxidizing activity was found to be most thermostable.