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Biomedical subjects

M Del Zompo

Publications and source records attributed to M Del Zompo.

At least 37 records · Page 2Linked to original sources
PubMed1993

Differential interaction of 1-methyl-4-phenylpyridinium ion with the putatively vesicular binding site of [3H]tyramine in dopaminergic and nondopaminergic brain regions.

The neurotoxin 1-methyl-4-phenylpyridinium ion (MPP+) in the brain striatum has recently been shown to bind at a putatively vesicular site labeled by [3H]tyramine ([3H]TY). Whereas in the rat and mouse striatum MPP+ antagonized TY binding competitively, in the cerebellum there was a mixed-type antagonism, which suggests the simultaneous occupancy of two different sites. Ki values from displacement curves revealed a fourfold difference in the affinity of MPP+ for TY sites in the two brain regions. The degeneration of central noradrenergic terminals induced by an intraperitoneal injection of the toxin N-(2-chloroethyl)-N-ethyl-2- bromobenzylamine in rats decreased by 80% the maximal number of cerebellar TY binding sites, while not affecting striatal binding. Furthermore, guanethidine, a marker for noradrenaline (NA) vesicles, potently inhibited TY binding in NA-innervated regions, such as the cerebellum and the parietal cortex, and poorly in the striatum. It is concluded (a) that both MPP+ and TY may also label NA vesicles and (b) that the vesicular carriers for dopamine and NA have different characteristics, which may underlie a regional specificity in the rate of endovesicular sequestration of MPP+, with either neurodegenerative or neuroprotective consequences, depending on the brain area involved.

1-Methyl-4-phenylpyridinium↗
PubMed1993

Selective MPP+ uptake into synaptic dopamine vesicles: possible involvement in MPTP neurotoxicity.

1. In the present study we provide evidence for a saturable, Mg2+/ATP- and temperature-dependent, tetrabenazine-, dopamine-, and amphetamine-sensitive uptake of 1-methyl-4-phenylpyridinium ion (MPP+) in synaptic vesicles from mouse striatum. 2. Similarity in the properties of the vesicular uptake suggests that in the striatum dopamine and MPP+ share the vesicular carrier. 3. The presence of MPP+ vesicular uptake in dopamine-rich regions such as striatum, olfactory, tubercles and hypothalamus, as well as its absence in cerebellum, cortex and pons-medulla, suggest that monoamine vesicular carriers differ between highly and poorly dopamine-innervated regions. 4. The restriction of active MPP+ uptake to the dopaminergic regions, which reflects the previously shown distribution of [3H]-MPP+ binding sites in mouse brain membranes, indicates MPP+ as a marker of the vesicular carrier for dopamine in dopaminergic neurones. 5. A role in MPP+ neurotoxicity is suggested for this region-specific, vesicular storage of the toxin.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

A double-blind study of L-sulpiride versus amitriptyline in lithium-maintained bipolar depressives.

A double-blind group comparison study of L-sulpiride and amitriptyline was carried out in 30 bipolar outpatients on maintenance treatment with lithium suffering from a major depressive recurrence. L-sulpiride showed equivalent antidepressant activity to amitriptyline at 4 weeks using the Hamilton Rating Scale for Depression. However, the onset of action was faster in the L-sulpiride group, showing a significant improvement at 1 week in both anxiety-somatization and specific depression items, including depressed mood, feelings of guilt, work & activities and retardation. The incidence of anticholinergic side effects was significantly higher in the amitriptyline treatment group.

Ambulatory Care↗
PubMed1992

Characterization of a putatively vesicular binding site for [3H]MPP+ in mouse striatal membranes.

[3H] N-Methyl-4-phenylpyridinium ion (MPP+) binds with a fully reversible, high affinity process to a population of sites mainly localized in the mouse striatum (Bmax = 168 +/- 15 fmol/mg protein, KD = 1.4 +/- 0.4 nM). The majority of specifically-bound radioactivity was localized in the synaptosomal fraction. Unilateral, striatal denervation with 6-hydroxydopamine (6-OHDA) markedly (by 65-70%) decreased the number of [3H]MPP+ sites. Besides dopamine, the vesicular markers tyramine, tetrabenazine and reserpine inhibited [3H]MPP+, while mazindol was a poor displacer. Adenosine triphosphate (ATP) and Mg(2+)-ions did not affect [3H]MPP+ binding. It is concluded that these sites may represent a marker of striatal storage vesicles for dopamine.

1-Methyl-4-phenylpyridinium↗
PubMed1992

Localization of MPP+ binding sites in the brain of various mammalian species.

The distribution and density of 3H-MPP+ binding sites were studied by in vitro quantitative autoradiography in the brain of the mouse, rat and monkey. The highest levels of 3H-MPP+ specific binding were observed in rat brain. The substantia nigra in rat and monkey, and the anterior caudate-putamen formation in mouse and monkey showed the lowest density of autoradiographic grains. The presence of a relatively high density of MPP+ sites in the hippocampus of all species studied could be of interest to explain some effects of MPTP administration on convulsions caused by chemoconvulsants. The finding of a 60-70% reduction of 3H-MPP+ binding sites in the rat caudate-putamen, on the side of quinolinic acid infusion and no changes after 6-hydroxydopamine lesion of dopaminergic nigrostriatal neurons suggests the presence of these sites mainly on striatal cells. The results suggest that the distribution of MPP+ binding sites in brain would not seem to be related to MPTP toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1992

The course of thyroid abnormalities during lithium treatment: a two-year follow-up study.

A total of 116 patients on lithium treatment were followed up for 2 years to determine the course and the clinical relevance of thyroid abnormalities. Elevated thyroid-stimulating hormone (TSH) concentrations were transitory in most patients, except those with serum antithyroid antibodies. The patients who initially had microsomal antibodies remained positive, with an increase in titre in two-thirds of cases. Three young patients of both sexes developed thyroid autoimmunity early in the treatment. The risk of developing hypothyroidism was higher in women, especially in the presence of antibodies. TSH concentrations were significantly lower when carbamazepine was combined with lithium.

Adult↗
PubMed1991

Interaction of 1-methyl-4-phenylpyridinium ion and tyramine with a site putatively involved in the striatal vesicular release of dopamine.

The neurotoxin MPP+ potently inhibited the striatal binding of [3H]-tyramine, a putative marker for the vesicular transporter of dopamine, and provoked a massive in vivo release of striatal dopamine. Tetrabenazine, an established ligand for the vesicular catecholamine carrier, potently inhibited [3H]-tyramine binding, tyramine-provoked striatal efflux of dopamine and the fast component of MPP(+)-induced dopamine release. It is concluded that MPP+ in the striatum, besides interacting with additional intracellular targets, avidly binds at a vesicular site functionally involved with the outward transport of dopamine.

Animals↗
PubMed1991

Thyroid abnormalities during lithium treatment.

Thyroid function was evaluated in 150 Sardinian outpatients at different stages of lithium treatment. A visible and/or palpable goitre was found in 51% of patients, and there was no apparent correlation with the duration of treatment. No cases of symptomatic hypothyroidism were observed, but subclinical hypothyroidism was present in 19% of patients. The prevalence of specific antithyroid antibodies was positively correlated with age and duration of lithium treatment, and was higher in women. Subclinical hypothyroidism was observed in 53% of antibody-positive lithium-treated patients. Carbamazepine in combination with lithium was associated with significantly lower levels of total T4 and T3 than with lithium alone, and the ratios between total and free hormones were also decreased.

Adult↗
PubMed1990

Familial rates of affective illness in Sardinia with special reference to schizoaffective disorder.

Familial rates of psychiatric disorders were studied in southern Sardinia and showed an increase in relatives of probands with the following research diagnostic criteria (RDC) diagnoses: normal, unipolar depression, schizoaffective depressive, schizoaffective bipolar, bipolar with mania and bipolar with hypomania. A significantly higher risk for bipolar schizoaffective disorder was observed in relatives of bipolar schizoaffectives compared with relatives of normal probands.

Adult↗
PubMed1990

[3H]1-methyl-4-phenyl-2,3-dihydropyridinium ion binding sites in mouse brain: pharmacological and biological characterization.

Because 1-methyl-4-phenyl-2,3-dihydropyridinium ion (MPP+) appears to damage the dopaminergic neuron and cause neuronal death, we characterized [3H]MPP+ binding sites in mouse brain membranes. Among several compounds tested, debrisoquin [3,4-dihydro-2(1H)-isoquinolinecarboxamidine] and some analogues were able to antagonize [3H]MPP+ binding. Debrisoquin is able to block adrenergic transmission and inhibit the activity of monoamine oxidase A (MAO-A). We found a certain correlation between the ability of these agents to displace [3H]MPP+ from its binding sites and their capacity to inhibit MAO-A activity. These data and the finding of a higher number of [3H]MPP+ binding sites in human placenta compared to mouse brain suggest that these sites may correspond to MAO-A enzymes. Recently it has been demonstrated in human brain that neurons in regions rich in catecholamines are positive for MAO-A. Accordingly, we suggest MAO-A as a possible accumulation site of MPP+ within the dopaminergic neuron. We also indicate the chemical structural requirement associated with the best binding of debrisoquin analogues with [3H]MPP+ sites. It would be reasonable to test the effects of debrisoquin-like drugs able to pass the blood-brain barrier on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxicity.

Animals↗
PubMed1988

Evaluation of the toxicity of the dopaminergic neurotoxins MPTP and MPP+ in PC12 pheochromocytoma cells: binding and biological studies.

This study was designed to investigate the toxicity of both MPTP and MPP+ using some simple cell systems, such as PC12 and C6 cultures, as models. Exposure of PC12 cells to 0.5 mM MPTP for 72 h resulted in a 50% cell loss with respect to the control cells, and clorgyline, a MAO-A inhibitor, antagonized this toxic effect. Higher concentrations of MPTP demonstrated only a weak cytostatic effect on C6 cells. Moreover, MPP+ showed a toxic effect which was 100 times more evident than MPTP toxicity in the PC12. We found a single, saturable class of [3H]MPP+ binding sites with a relatively high affinity both in PC12 and C6 cell lines. Moreover, the most susceptible cell line towards the toxic effects of both MPTP and MPP+, i.e. PC12, has the higher number of MPP+ binding sites. Our results suggest that MPTP can be toxic not only via MAO-B, but also via MAO-A activity and we propose PC12 as a model to study the intracellular mechanisms of MPTP and MPP+ toxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Covalent protein binding of a metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine to mouse and monkey brain in vitro and in vivo.

We have recently reported that a reactive metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is formed in rat brain in vitro by type B monoamine oxidase (MAO). In the present study, we further characterize the irreversible binding in vitro using tissues from mice and monkeys, two species more sensitive than rats to MPTP neurotoxicity. We also report the occurrence of irreversible binding of radioactivity after administration of tritiated MPTP in the same species in vivo. Tissue homogenates were incubated at 37 degrees with 1-[methyl-3H]MPTP in in vitro experiments. Animals were injected with labeled MPTP and sacrificed at different times in in vivo experiments. The perchloric acid precipitates of tissue homogenates from either procedure were washed exhaustively with organic solvents and counted for radioactivity. The amount of recovered radioactivity in in vitro experiments was similar using brain homogenates from mice and monkeys, whereas a considerably lower amount was found in mouse liver. MAO-B inhibitors decreased the covalent binding. However, the combined MAO-B/MAO-A inhibitor pargyline had no effect if added after 2 hr of incubation. Sulfhydryl-containing compounds decreased the covalent binding in a concentration-related manner. GSH reduced the rate of the reaction throughout the incubation. The covalent binding slowly increased in time in vivo in mouse brain, not in liver. There was a two-fold variation of covalently bound radioactivity in different brain areas of 3H2-MPTP-treated monkey. This reactive metabolite may play a role in MPTP neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗