Molecular biology of neurological and psychiatric disorders. I. Effect of parkinsonism, age, sex and L-dopa on platelet monoamine oxidase

Abstract

Since there is substantial evidence for a nigrostriatal dopamine defect in Parkinson's disease and since monoamine oxidase (MAO) appears to be essential for the degradation of dopamine, we investigated whether this enzyme is involved in the pathogenesis of this disease or in the therapeutic action of L-dopa. To gain a solid basis for our analysis we studied some properties of platelet MAO, at present the only practical in vivo source for human MAO. Substrate and inhibitor pattern clearly pointed to a predominant B-type character of this enzyme. By using 3 substrates, m-iodobenzylamine, p-methoxybenzylamine, and tyramine, we found a marked age and sex difference in MAO activity. In untreated parkinsonian patients, platelet MAO was slightly reduced as compared with age- and sex-matched controls. Treatment with L-dopa induced a further reduction of platelet MAO activity in both sexes, but more in men than in women. We conjecture that the action of L-dopa on parkisonian patients is twofold: L-dopa is known to enhance the release of gonadotropins and thus to increase the production of sex hormones which in turn are capable of reducing MAO activity. Dopamine, formed from L-dopa, may thus have a better chance for survival in reaching the dopaminergic receptor. A new form of therapy, based on this concept, is proposed.

Platelet monoamine oxidase activity in Huntington's chorea.

“…Alterations in the activity of this intraneuronal enzyme can affect free intracellular amine levels and uptake from the intrasynaptic cleft (Hughes, 1972). Platelet monoamine oxidase activity may be altered in diseases affecting the central nervous system, for example, Parkinson's disease (Zeller et al, 1976), migraine (Sicuteri et al, 1972;Glover et al, 1977a) affective disorders (Murphy and Weiss, 1972;Landowski et al, 1975), and schizophrenia (Wyatt and Murphy, 1976). These conditions have amine disorders as a common suggested feature.…”

Platelet Monoamine Oxidase B Activity in “de novo” and L-Dopa Treated Parkinsonian Patients and Controls

“…Mann et al" found no differences. Zeller et al 12 indicated lower (not significant) MAO-B activity in PD, using tyramine as substrate. Significantly increased activity of MAO-B in untreated 13 …”

“…Animal studies have indicated that MAO-A is mainly, but not exclusively, located in brain neurons, such as neurons of the locus coerulus, while MAO-B is preferentially found in serotonergic neurons, glia and astrocytes. 12 Elevated levels of MAO-B were found in the substantia nigra of parkinsonian patients. Estimation of peripheral blood cell activities of monoamine oxidase B may reflect central enzyme activity.…”

Human platelet protein kinases in diabetic retinopathy

“…Blood was obtained from patients with pro~ferative diabetic retinopathy in siliconized tubes containing 3.8% sodium citrate. Platelets were collected and lysed according to Zeller et al [3] . A platelet count was obtained using the Codter counter.…”