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Biomedical subjects

M Trabucchi

Publications and source records attributed to M Trabucchi.

At least 325 records · Page 18Linked to original sources

Effect of right middle cerebral artery occlusion on striatal dopaminergic function.

Following right middle cerebral artery occlusion in the rat, striatal dopaminergic system alterations were studied. Dopamine turnover was assessed by measuring 3,4-dihydroxyphenylacetic acid concentrations and dopamine receptor function, by measuring (3H)-Spiroperidol binding. There was a transient decrease in 3,4-dihydroxyphenylacetic acid and permanent damage to dopamine receptors, as indicated by a time-dependent progressive reduction in the number of (3H)-Spiroperidol binding sites. The receptor deficit also manifested as turning behaviour towards the lesioned side 4 weeks after the lesion following subcutaneous apomorphine. Long-term changes of dopaminergic receptor activity in this experimental model of cerebral infarction may be secondary to cortical degeneration following middle cerebral artery occlusion.

3,4-Dihydroxyphenylacetic Acid↗

Central toxic effects of chronic ethanol treatment: actions on GABA and benzodiazepine recognition sites.

Prolonged ethanol treatment modifies various neurotransmitter systems. GABAergic neuronal function was particularly affected. On the other hand, clinical reports have indicated an interaction between ethyl alcohol and benzodiazepine receptors. These observations suggest a possible site of action of ethanol at the level of the GABA-benzodiazepine receptor complex. Our results showed that ethanol treatment differentially affected GABA receptor function and benzodiazepine binding sites. When [3H]GABA binding in the cerebellum, striatum and hippocampus was increased, [3H]diazepam binding remained unchanged in the same areas. The possibility of modulation of ethanol effects on GABAergic neurons through benzodiazepine receptors is discussed.

Animals↗

"On-off" phenomena, dyskinesias and dystonias. Comparison of lisuride versus apomorphine acute treatment.

In this study the effects of an acute injection of lisuride and apomorphine in 12 subjects affected by dystonic-dyskinetic syndromes of different aetiology are evaluated: 3 patients with spasmodic torticollis, 4 with tardive dyskinesia and 5 Parkinson patients suffering from "on-off" attacks with prominent dyskinesias during the mobile phase. In the last group drugs were administered during the "on" phase. In 11 out of 12 patients both lisuride and apomorphine induced a marked improvement of the abnormal involuntary movements. In Parkinson and torticollis patients both drugs also reduced the rigidity. In comparison to apomorphine, lisuride showed a more effective and long-lasting action. Only in one Parkinson patient did the drugs fail in showing any change.

Apomorphine↗

Characterization of beta-adrenergic receptors on human cerebral microvessels.

Cerebral microvessels were separated and prepared from human brain cortex by albumin floatation and glass bead filtration. The binding of a specific beta-adrenergic antagonist, (125I) iodohydroxybenzylpindolol, to the microvessel preparation was characterized by high affinity, saturability, and stereospecificity. The presence of specific beta-adrenergic receptor sites in human cerebral microvessels supports the hypothesis of adrenergic regulation of the function of cerebral microvessels.

Brain↗

Subtypes of beta-adrenergic receptors in rat cerebral microvessels.

The 125I-labeled iodohydroxybenzylpindolol (IHYP) binding to beta-receptors on brain micro-vessels is inhibited by isoproterenol, epinephrine and norepinephrine, with Ki values of 2 X 10(-7) M, 2.5 X 10(-6) M and 1.2 X 10(-5) M, respectively. A modified Scatchard analysis of the inhibitory effects of practolol, metroprolol and zinterol on IHYP binding has shown that the proportion of beta 2-receptors in our preparation is about 80% of the total beta-adrenergic receptor population. Our data indicate that the beta-adrenergic receptors located on cerebral microvessels are of both beta 1 and beta 2 types, with a predominance of the beta 2 type.

Animals↗

Chronic lead treatment induces in rat a specific and differential effect on dopamine receptors in different brain areas.

There is now evidence that two classes of dopaminergic receptors are present in CNS of the rat: D1, associated, and D2, not associated with adenylate cyclase activity. Drugs which interact specifically with D2 receptor are more capable of antagonizing the hyperkinetic behavior induced by lead exposure in rat. They also have a beneficial effect in children with hyperkinetic disorders. We found that the dose (-)sulpiride which causes sedation is lower in lead intoxicated animals than in controls. On the contrary, haloperidol produces sedation with the same potency in lead-treated and in control rats. The reported behavioral effects were found to be correlated with biochemical changes. In fact, in lead exposed rats D2 receptors, measured by (-)-[3H]sulpiride stereospecific binding, are altered, while D1 receptors seem not to be affected. The alterations are different according to the area examined: D2 receptor function is increased in the striatum and decreased in the nucleus accumbens. The impairment of D2 receptor might explain the better capacity of substituted benzamides to improve the hyperkinetic behavior observed in lead exposed rats.

Adenylyl Cyclases↗

Ethanol-induced changes of dopaminergic function in three strains of mice characterized by a different population of opiate receptors.

The effects of ethanol have been studied in three strains of mice (DBA 2J, albino, and C57 BL/6J) having different populations of opiate receptors. Acute ethanol treatment induces a significant increase in striatal dopamine metabolism only in the mouse strains (C57 and albino) that are rich in enkephalinergic receptors upon nigrostriatal dopaminergic fibers. After chronic ethanol, the same strains develop tolerance to striatal dihydroxyphenylacetic acid increase, while the striatal dopaminergic recognition sites become supersensitive. DBA mice, which have lower numbers of enkephalinergic receptors and higher levels of enkephalins in the striatum, fail to show changes in central dopaminergic function after acute or chronic ethanol treatment. Our results indicate the importance of an interaction between ethanol and opiate receptors in determining the neurochemical and behavioral effects of ethanol.

Animals↗

Rat dopaminergic function in the retina during aging.

Parameters of dopaminergic transmission were studied in the retina of mature (3-4 months) and aged (23-24 months) rats. In the retina of senescent rats were found significantly higher dihydroxyphenylacetic acid (DOPAC) levels and a higher number of (3H-)spiroperidol binding sites. We detected also an increase of (3H)- methionine-enkephalin binding sites. The changes in the density of (3H)-spiroperidol and (3H)-Metenkephalin binding sites in the retina are opposite to those observed in the brain of aged rats.

3,4-Dihydroxyphenylacetic Acid↗

Identification of beta-adrenergic receptor binding sites in rat brain microvessels, using [125I]iodohydroxybenzylpindolol.

Brain microvessels were prepared from rat cerebral cortex. The purity was confirmed by phase-contrast microscopy and by the measurement of an enzymatic marker, gamma-glutamyltranspeptidase. The microvessel preparation was subjected to radioreceptor assay using a 125I-labelled beta-adrenergic antagonist, hydroxybenzylpindolol (IHYP). The binding was linear with protein concentration up to at least 80% microgram per tube. It was saturated at 200 pM IHYP concentration. The KD value calculated by Scatchard analysis was 69.4 +/- 9.9 pM. The maximum binding (Bmax) was 107 +/- 4 fmol/mg protein. The binding reached equilibrium within 30 min and was dissociated by addition of (-)-propranolol. The inhibitory effects of isomers of propranolol and isoproterenol on this binding showed that (-)-isomers were two orders of magnitude more potent than the (+)-isomers. Other neurotransmitters did not affect IHYP binding. The characteristics of the binding, saturability, high affinity, reversibility and stereospecificity, suggest tha IHYP is bound to beta-adrenergic receptor sites located on brain microvessels.

Animals↗

Sulpiride and the role of dopaminergic receptor blockade in the antipsychotic activity of neuroleptics.

It is now generally recognized that dopamine receptors exist in the CNS as different subtypes: D1 receptors, associated with adenylyl cyclase activity, and D2 receptor, uncoupled to a cyclic AMP generating system. In order to understand the role of D1 and D2 receptors in the antipsychotic action of neuroleptics, we have performed subchronic treatment with haloperidol, a drug which acts on D1 receptors, and sulpiride, a selective antagonist to D2 receptors. Long-term treatment with haloperidol does not induce significant supersensitivity of the D2 receptors. In fact under these conditions 3H-(-)-sulpiride binding, which is a marker of D2 receptor function, does not increase in rat striatum, while the long-term administration of sulpiride itself produces supersensitivity of D2 receptors. Moreover, sulpiride does not induce supersensitivity of the D1 receptors, characterized by 3H-spiroperidol binding. These data suggest that both types of dopamine receptors may be involved in the clinical antipsychotic effects of neuroleptics. Unilateral lesion of the nigrostriatal dopaminergic pathway produces an increase of striatal dopaminergic receptors, measured either by 3H-spiroperidol and 3H-(-)-sulpiride binding. These findings suggest that D1 and D2 receptors are present in postsynaptic membranes while it is still not known whether they exist in the same cellular elements.

Adenylyl Cyclases↗

Evaluation of endorphin content in the CSF of patients with trigeminal neuralgia before and after Gasserian ganglion thermocoagulation.

The beta-endorphin content in cerebrospinal fluid (CSF) was evaluated in 10 patients with idiopathic trigeminal neuralgia during medical treatment (with or without carbamazepine) and after selective thermocoagulation of the Gasserian ganglion. These values were compared with those obtained in a control group of seven patients without pain problems. No statistically significant difference was found between patients suffering from trigeminal neuralgia and those without pain. Furthermore, neither pharmacological treatment nor surgery changed CSF endorphin values. It is concluded that there is no pathogenetic relationship between trigeminal neuralgia and endorphins.

Adult↗

Aging process affects a single class of dopamine receptors.

[3H]Spiroperidol and [3H](-)-sulpiride specific binding have been used to assay for D1 and D2 dopaminergic recognition sites in striatal membranes of aged rats. While [3H]spiroperidol binding shows a decreased number of binding sites, no changes have been detected in [3H](-)-sulpiride binding, which is a marker for D2 dopaminergic receptors. Data obtained with GTP and DA-dependent adenylyl cyclase activity confirm the hypothesis that aging selectively affects in rats those dopaminergic receptors coupled to the formation of cyclic AMP (D1).

3,4-Dihydroxyphenylacetic Acid↗