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Biomedical subjects

B A Callingham

Publications and source records attributed to B A Callingham.

At least 73 records · Page 4Linked to original sources
PubMed1980

The influence of benserazide on changes in monoamine oxidase activity in some rat tissues following treatment with L-DOPA.

1. This study was designed to see whether or not increases in monoamine oxidase (MAO) specific activity that follow chronic treatment of rats with L-dihydroxyphenylalanine (L-DOPA) could be modified by benserazide (Ro 4-4602), an inhibitor of L-aromatic amino acid decarboxylase, and to compare the properties of the increased MAO activity with those of control animals. 2. Male wistar rats were treated with L-DOPA (250 mg/kg) and benserazide (40 mg/kg) either alone or in combination for 10 days. 3. The activity of MAO in homogenates of heart, kidney, liver and brain was measured with 5-hydroxytryptamine (5-HT) and benzylamine (BZ). 4. The significant increases in MAO specific activity seen in heart and kidney following L-DOPA treatment could be reduced or prevented by benserazide. 5. Use of the selective MAO inhibitor clorgyline showed that the increases in MAO specific activity, when measured with either 5-HT or BZ were due to an increase in the number of active centres of MAO-A, in the rat heart. 6. There was a significant increase in the Vmax of the enzyme reaction with 5-HT, in the rat heart and kidney homogenates. 7. It is concluded that L-DOPA increases the specific activity of MAO-A in rat heart and kidney as a result of its decarboxylation.

Animals↗
PubMed1980

The binding of [3H] pargyline to rat liver mitochondrial monoamine oxidase.

The synthesis and purification of tritium labelled N-desmethylpargyline and pargyline are described. The suitability of these irreversible suicide inhibitors of monoamine oxidase (MAO) as ligands in binding studies to rat liver mitochondrial MAO has been evaluated. [3H] Pargyline was found to be more satisfactory than its N-desmethyl analogue because of its greater potency and lower proportion of non-specific binding. The binding of pargyline reached saturation when about 31 pmol mg protein-1 was bound. It was not possible to explain the time course of the binding by either simple first or second-order kinetics. [3H]-Pargyline is a potentially valuable ligand for the estimation of the concentration of NAO active centres without the need to remove the enzyme from the mitochondrial membrane.

Animals↗
PubMed1980

Some factors influencing the metabolism of benzylamine by type A and B monoamine oxidase in rat heart and liver.

The ability of MAO-A and MAO-B to metabolize benzylamine in vitro has been investigated in mitochondrial preparations from rat liver and heart. Although under normal circumstances benzylamine appeared to be metabolized exclusively by MAO-B in the rat liver, a contribution by both MAO-A and a clorgyline-resistant enzyme component was revealed when the MAO-B activity was much reduced by pretreatment of the mitochondria with appropriate concentrations of deprenyl. These three enzyme activities also contributed to benzylamine deamination in rat heart mitochondria. However, binding studies with [3H]pargyline, which provided an estimate of the respective concentrations of MAO-A and MAO-B active centres in heart mitochondria, indicated a ratio between MAO-A and MAO-B, markedly different from that shown by plots of inhibition of benzylamine metabolism by various concentrations of clorgyline. The interpretation of these clorgyline plots is discussed in terms of the kinetic constants of both MAO-A and MAO-B, and the relative amounts of each enzyme. It is proposed that although the turnover rate constant for benzylamine metabolism by MAO-A is much smaller than that shown by MAO-B, in those tissues containing a large ratio of MAO-A:MAO-B content, the metabolism of benzylamine by MAO-A can be detected.

Amines↗
PubMed1979

Role of catecholamines in hypotensive response to dieting.

The effect of dieting on blood pressure and catecholamine metabolism was assessed in 11 normotensive obese women by providing first a weight-maintenance regimen high in carbohydrate and then a low-energy diet. All dietary constituents other than carbohydrate were maintained constant throughout the 18-day study. The low-carbohydrate diet led within 48 hours to a 41% fall in the urinary output of 4-hydroxy-3-methoxy mandelate and a significant fall in systolic and diastolic blood pressure. Plasma noradrenaline concentrations also fell and the hypotensive effect of the diet continued despite a maintained total body sodium. Thus the fall in blood pressure appeared to be mediated by changes in catecholamine metabolism independent of sodium intake. This may explain both the usefulness of weight reduction in hypertensive patients and the fainting that occurs in some normotensive obese subjects taking slimming regimens low in carbohydrate.

Adult↗
PubMed1979

Selective influences of age and thyroid hormones on type A monoamine oxidase of the rat heart.

The specific actiivty of rat heart MAO, towards both tyramine and benzylamine as substrates, was found to increase with the age of the animal, and also after administration of (-)-thyroxine to young male rats. Conversely, enzyme activity was decreased in animals made hypothyroid by including 2-thiouracil in their diet. However, with both age and altered thyroid status, relatively greater changes in the deamination of tyramine rather than in that of benzylamine, were obtained. Clorgyline and deprenyl, used as inhibitors of rat heart MAO, indicated that tyramine is metabolized solely by MAO-A, whereas benzylamine is a substrate for both MAO-A and -B, and also a clorgyline- and deprenyl-resistant enzymic activity. The proportional contribution of MAO-A, -B and the clorgyline-resistant enzyme towards the total benzylamine deamination in the rat heart was found to vary with the age and with altered thyroid status of the animal in such a way that selective changes in the activity of MAO-A appear to be largely responsible for the overall changes in the specific activity of rat heart MAO which occur in response to these developmental factors.

Aging↗
PubMed1978

The inhibition by clorgyline of 5-hydroxytryptamine deamination by the rat liver.

The inhibition of the monoamine oxidase activity in the rat liver by the substrate selective inhibitor clorgyline has been investigated with 5-hydroxytryptamine as substrate. The results obtained are consistent with a theoretical model whereby the inhibition of enzyme activity by clorgyline follows a reversible association phase leading to an irreversible 'suicide' reaction. The relative concentrations of enzyme and inhibitor are of the same order, and can account both for the failure of the reaction to go to completion, and for the differences in the apparent sensitivity of enzyme preparations to inhibition by clorgyline. The possible value of this type of inhibition as a means of assay for monoamine oxidase active centres is discussed.

Animals↗