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Biomedical subjects

V Glover

Publications and source records attributed to V Glover.

At least 163 records · Page 9Linked to original sources

Platelet monoamine oxidase: specific activity and turnover number in headache.

Monoamine oxidase turnover numbers (molecules of substrate converted to product per minute per active site) have been calculated for the human platelet enzyme using [3H]pargyline. Headache patients with high and low monoamine oxidase specific activities relative to controls were found to have turnover numbers very close to those for controls. This finding suggests that their specific activities vary because of differences in the concentration of active monoamine oxidase molecules, rather than differences in the ability of those enzyme molecules to catalyse the deamination reaction.

Binding Sites↗

Multiple forms of phenolsulphotransferase in human tissues: selective inhibition by dichloronitrophenol.

Evidence is presented for two functional forms of phenolsulphotransferase in human tissues: (1) activity ratios, using dopamine and phenol as substrates, varied 30-fold between different tissues, whereas the dopamine to tyramine activity ratio was relatively constant; (2) incubation at 37 degrees caused a selective decrease in activity towards dopamine compared with phenol; and (3) phenol sulphoconjugation was selectively inhibited by dichloronitrophenol and pentachlorophenol compared with that of dopamine and tyramine. The two forms, which have been designated M (monoamines) and P (phenol), were both present in platelets, jejunum, adrenal and brain.

Arylsulfotransferase↗

Platelet phenolsulphotransferase deficiency in dietary migraine.

Patients with dietary migraine were found to have significantly lower levels of platelet phenolsulphotransferase activity than either migrainous patients without a history of dietary provocation or normal controls. Of the two known human variants of this enzyme, the phenol-inactivating P form, for which no endogenous substrate has so far been identified, was more severely involved than the M enzyme, which inactivates monoamines (including tyramine). Such commonly implicated dietary triggering agents as chocolate and cheese may contain as-yet-unidentified phenolic substrates of phenolsulphotransferase P; if the platelet enzyme deficiency were mirrored by low gut activity, abnormally large amounts of potentially toxic substances might gain access to the circulation in consequence.

Adult↗

beta-Carbolines as selective monoamine oxidase inhibitors: in vivo implications.

The inhibitory action of a range of beta-carbolines on human and rat monoamine oxidase (MAO) A and B has been studied. Concentrations of 5-hydroxytryptamine and phenylethylamine, approximately at their Km values, were used as substrates for MAO A and B respectively. A wide variation in selectivity was found, with harmaline being 10,000 times more potent an inhibitor of A than B whereas, using tetrahydro-beta-carboline and harmane, the difference was nearer to ten-fold. Of the carbolines which have been found endogenously, tetrahydro-beta-carboline, 6-methoxytetrahydro-beta-carboline and harmane are all sufficiently potent inhibitors of human MAO A, with I50 values of 5 X 10(-6), 10(-6), 5 X 10(-7) M respectively, for this property to be of possible physiological significance. Harmane, with an I50 of 5 X 10(-6) M, might also play a role as an inhibitor of MAO B.

Animals↗

Platelet size: no correlation with migraine or monoamine oxidase activity.

A Coulter Model "S Plus" counter has been used to study platelets from 39 migrainous patients between attacks, six during attacks, eight with active cluster headache and 26 controls. None of the patient groups showed any abnormality in platelet size profile. There was no correlation between platelet monoamine oxidase activity and mean platelet volume in any of the groups.

Adult↗

Raised endogenous monoamine oxidase inhibitor output in postwithdrawal alcoholics: effects of L-dopa and ethanol.

Urinary output of endogenous monoamine oxidase inhibitor was significantly greater in a group of postwithdrawal alcoholics than in controls. An oral dose of 0.5 g of L-dopa reduced output to control values in the alcoholics, but in the controls themselves output was unaffected. A similar excretion pattern to unextracted samples was observed in ethyl acetate extracts of these urine samples, acidified to pH 1. In a second group of postwithdrawal alcoholics, where the L-dopa effect was confirmed, ethanol administration brought about a small but not significant reduction in inhibitor output.

Adult↗

Human platelet phenolsulphotransferase: separate control of the two forms and activity range in depressive illness.

Human phenolsulphotransferase exists in two forms, one specific for dopamine and tyramine, termed "M" and one for phenol, termed "P". In this study we have shown that these two forms are under separate control by correlating their activities in different individuals using different substrates. There was a highly significant correlation between the activities with dopamine, p-tyramine and 4-hydroxy-3-methoxyphenylglycol, but no significant correlation between the activities with any of these three substrates and that with phenol. Neither age nor sex had any effect on platelet phenolsulphotransferase "M" or "P" activities. Nor was there any significant correlation between platelet monoamine oxidase activity and phenolsulphotransferase "M" or "P" activities. Human platelet phenolsulphotransferase "M" was found to be unstable at temperatures above 35 degree C and it lost substantial activity when stored deep frozen in isotonic saline. However it was stable for up to four months when stored in isotonic sucrose or 10 mmol/l phosphate buffer (pH 7.4). Phenolsulphotransferase "M" amd "P" activities were measured in platelets from depressed patients of a diagnostic type characterized by low output of tyramine-O-sulphate after oral tyramine loading but their enzyme activities were not different from those in two control groups.

Arylsulfotransferase↗

Sulphate conjugation of biologically active monoamines and their metabolites by human platelet phenolsulphotransferase.

The substrate specificity of phenosulphotransferase in human platelets has been studied using a wide range of biogenic amines and their metabolites. Substantially differing activities were observed at 30 mumol/l; the enzyme was more active towards the catecholamines and their alcoholic metabolites than the corresponding acids (with the exception of 3,4-dihydroxyphenylacetic acid which did not appear to be a substrate) and the relative order was not changed by dialysis to remove possible low molecular mass inhibitors. However, most of the V values were similar to each other, reflecting a large variation if Km values, ranging from 0.3 mumol/l for 3-methoxytyramine to 3700 mumol/l for 4-hydroxy-3-methoxymandelic acid. All substrates showed substrate inhibition. Dopamine, noradrenaline and adrenaline all had a high affinity for the enzyme, with Km values of 3.0, 5.0 and 2.7 mumol/l respectively. These values are considerably lower than those for monoamine oxidase and the relative importance of oxidation and sulphoconjugation of these amines in vivo may be concentration dependent. Human platelet phenolsulphotransferase appears different from the rat enzyme, but similar to that described by others in human brain. The platelet should be a useful source of enzyme for clinical studies.

Arylsulfotransferase↗

Brain monoamine oxidase activity in schizophrenics and controls.

Postmortem samples of caudate nucleus and frontal cortex from schizophrenic, schizophrenic-like, and control subjects were examined for monoamine oxidase activity using dopamine, phenylethylamine, and 5-hydroxytryptamine as substrates. There were no significant differences between the diagnostic groups with any of the three substrates. Neither was there a difference between the sexes, nor a consistent relationship of enzyme activity to age.

Aged↗

Increased platelet monoamine oxidase activity in affective disorders.

Platelet monoamine oxidase activity was determined in 52 unipolar depressive patients, 26 patients with bipolar affective disorder and 48 controls using phenylethylamine as substrate. Unipolar depressive patients of either sex and bipolar depressive women showed significantly higher platelet MAO activity than controls. Women had higher activity than men. Neither age nor serum lithium level correlated with enzyme activity and there was no significant change in activity after the institution of lithium treatment.

Adult↗

Is the failure of (-)deprenyl, a selective monoamine oxidase B inhibitor, to alleviate depression related to freedom from the cheese effect?

The selective monoamine oxidase (MAO) B inhibitor (-)deprenyl failed to produce any greater benefit than placebo in a limited double-blind trial conducted in depressive patients. Its relative freedom from the so-called cheese effect was confirmed, however, in drug-treated patients challenged IV with tyramine. There is evidence to suggest that this cheese effect, a facilitated tyramine-induced hypertensive response, is pharmacologically distinct from MAO inhibition proper. Thus, it is conceivable that its central counterpart, an enhanced noradrenaline release due to the access of traces of tyramine to the CNS, is a prerequisite for any therapeutic benefit obtainable with the MAO-inhibitory drugs in general.

Blood Pressure↗

The specific activity of platelet monoamine oxidase varies with platelet count during severe exercise and noradrenaline infusion.

During severe exercise or noradrenaline infusion in healthy male volunteers, the platelet count first rose and then fell. Platelet monoamine oxidase activity per unit protein rose and fell in parallel and the correlation with the platelet count was highly significant (P less than 0.001). The increase in observed specific monoamine oxidase activity might be due to the release of a population of platelets with higher specific activity, and the decrease to their selective removal.

Adult↗

Urinary MAO inhibitor in psychiatric illness.

Normal human urine contains an endogenous monoamine oxidase inhibitor. We have now investigated its activity in urine samples from psychiatric patients in various diagnostic categories. Significantly higher values were observed in alcoholics recently withdrawn from ethanol, compared with controls. Inhibitory activity was not specifically related to primary affective disorders. Inhibitor output may be positively related to certain symptom clusters rather than to disease entities (i.e. alcohol withdrawal, agitation, and hyperkinesis). Significantly lower inhibitor output was also found in a small group of patients with chronic schizophrenia.

Adolescent↗

Human platelet monoamine oxidase activity in health and disease: a review.

The most readily available source of monoamine oxidase in man is the platelet, although only the B form of the enzyme is represented in this site. Platelet activity is higher in women than in men. The enzyme activity is generally stable and is partly under genetic control. There is some evidence that individuals with low activity have a higher psychiatric morbidity than those with high activity. Despite some negative studies, the consensus of publication dealing with schizophrenia, migraine, and alcoholism find that mean platelet monoamine oxidase activity in the patient group is lower than in the controls. Values are raised in unipolar depression. Technical differences, or patient or control group heterogeneity, might well account for the absence of unanimity in the literature. A considerable degree of overlap between patient and control values, whatever the clinical diagnosis, appears to be the standard finding. Apart from these neuropsychiatric disturbances, platelet monoamine oxidase activity is raised in megaloblastic anaemia and reduced in iron deficiency anaemia. Although altered enzyme activity values may be linked to abnormal platelet populations in some of the haematological disorders discussed, in general the causes of abnormal platelet monoamine oxidase activity are unknown.

Adolescent↗

Platelet monoamine oxidase activity and headache.

Mean platelet monoamine oxidase activity was reduced compared with control values in groups of headache-free male (but not female) patients suffering from classical migraine and from tension headache. Mean activity in male cluster patients, headache free, both during acute and quiescent phases of their illness, was also notably reduced. Retesting some migraine subjects after up to four years, showed that low activity may be a persistent feature: the correlation coefficient for repeated assays was 0.91 (p less than 0.01). There was no relationship between platelet monoamine oxidase activity and history of dietary migraine. A subgroup of headache patients with permanently low monoamine oxidase activity values may have been defined.

Blood Platelets↗