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Biomedical subjects

M Trabucchi

Publications and source records attributed to M Trabucchi.

At least 235 records · Page 13Linked to original sources

Effect of chronic calcium antagonist treatment on dopamine recognition sites in rat striatum.

The effects of nimodipine and flunarizine administration (18 days 15 mg/kg/day p.o.) on striatal dopamine recognition sites in rats were investigated in vivo. In vitro flunarizine but not nimodipine displaces [3H]spiroperidol binding. After in vivo treatment both drugs induce a significant increase in the number of sulpiride displaceable spiroperidol binding sites (flunarizine, +114%, nimodipine +61%) concomitant with an increase in the dissociation constant. Binding parameters return toward control values after 1 week of suspension of the treatment. The results suggest that the repeated in vivo treatment with nimodipine and flunarizine may significantly interact with dopaminergic transmission leading to adaptive changes of the dopamine recognition sites.

Animals↗

L-type calcium channels are modified in rat hippocampus by short-term experimental ischemia.

Increasing evidence suggests a role for calcium ions in the pathophysiology of ischemic brain damage. The major mechanism allowing calcium entry from the extracellular compartment is the opening of voltage-operated calcium channels. In this line, we have explored the hypothesis that the characteristics of central L-type voltage-dependent calcium channels, labeled by the dihydropyridine ligand 3H-PN 200-110, may be modified by experimental ischemia. The results show that short-term mild ischemia, produced in the rat by 1 h of right carotid ligation, induces an increase in the number of 3H-PN 200-110 binding sites in the hippocampus ipsilateral to the side of carotid occlusion, accompanied by an increase in the dissociation constant value, whereas no changes in the kinetic parameters of the binding were observed in the other areas examined, i.e., the cortex and the striatum. The changes in hippocampus are transient: 96 h after the occlusion, binding parameters return to the control range. The modifications of the binding characteristics in the hippocampus may be related to alterations of Ca2+ fluxes through L-type calcium channels.

Animals↗

Reduced cAMP-dependent phosphorylation in striatum and nucleus accumbens of aged rats: evidence of an altered functioning of D1 dopaminoceptive neurons.

Cyclic AMP-dependent phosphorylation was measured in particulate and in cytosolic fractions of two brain dopaminergic areas, i.e., striatum and nucleus accumbens, of young (3 months) and old (24 months) rats. A reduced cAMP-stimulated 32P incorporation was observed in several protein bands in both brain areas in the aged group. In the soluble fraction the reduced phosphorylation of DARPP-32, which is specific for dopaminoceptive neurons bearing D-1 receptors, may be of particular relevance in the mechanisms of age-related changes in dopaminergic transmission.

Aging↗

Glial brain tumors lack microvascular adrenergic receptors.

In human and animal brain microvessels beta-adrenergic receptors have been identified which are suggested to subserve the regulation of capillary function in both physiological and pathological conditions. Brain tumors are supplied by vessels that differ from those supplying normal cerebral tissue in various structural and functional parameters. In order to study the characteristics of brain tumor microcirculation, we have investigated the presence of beta-adrenergic receptors in capillaries isolated from different types of neoplasms using the specific radioligand 125I-iodocyanopindolol (ICYP). The microvessels were isolated and prepared by albumin flotation and glass bead filtration from normal and pathological tissues. No ICYP-specific binding was detected in the microvessels of tumors of glial origin, while capillaries obtained from meningiomas and neurinomas showed, like the normal brain, a specific binding of the radioligand. The data indicate that the regulation of capillary function in glial tumors differs from that of normal cerebral tissue and extraparenchymal tumors, thus indicating an impaired control of the vascular permeability.

Brain Neoplasms↗

The central dopaminergic system: susceptibility to risk factors for accelerated aging.

The synaptic deficit of brain dopaminergic activity involves a complex pattern of changes both at presynaptic and at postsynaptic level. The aged dopaminergic nuclei present a reduced number of dopamine terminals, a decreased ability to synthesize and reuptake dopamine and defective recognition sites both in terms of absolute number of D2 receptors and of transducing mechanisms linked to D1 receptors. These changes suggest that the dopaminergic system may be particularly sensitive during aging to environmental, iatrogenic and toxic factors, which may easily make the elderly develop symptoms of central dopamine deficiency.

Aging↗

Aging modifies the asymmetry in brain microvascular regulation.

Cerebral ischemia induced by unilateral carotid occlusion in rats decreases in an asymmetric manner the number of beta-adrenergic receptors in microvessels prepared from cerebral cortexes ipsilateral and contralateral to the side of the ligature. In particular, the reduction is more pronounced in the left hemisphere in case of both right and left carotid ligature. The greater receptor decrease in the left side of the brain was shown to depend on the integrity of interhemispheric connections. We show that the changes in capillary beta-adrenergic receptors in response to unilateral carotid occlusion are qualitatively modified during aging. In particular, the asymmetry in the response pattern observed in young rats is lost. The mechanisms underlying this phenomenon may be based on an age-related impairment in the transfer of neuronal information between the two sides of the brain.

Aging↗

Erythrocyte 3H-ouabain binding and digitalis treatment in ethanol addicted patients.

The binding of 3H-ouabain to human erythrocytes was analyzed in a population of hospitalized male ethanol addicted patients under long term digitalis treatment. In the non-alcoholic patient group the long term digitalis treatment induced an increase in Bmax and Kd values; such modification was not observed in the alcoholic patients. Chronic alcohol intake itself induced an increase in 3H-ouabain kinetic parameters. These observations confirm that ouabain binding to human erythrocytes is subject to pharmacological and toxicological regulation and that adaptive changes in peripheral tissues can be useful in predicting possible parallel modifications in other less accessible tissues.

Adult↗

Concomitant regulation of hippocampal calcium antagonist receptors and calcium uptake by substance P.

The interaction of various neuropeptides with calcium antagonist binding was investigated in rat hippocampus. Among the peptides examined Substance P selectively increased the binding of phenylalkylamine and dihydropyridine calcium antagonists; this action was receptor mediated. No effect was observed with Substance P in other brain areas and with neurotensin and met-enkephalin in all the areas examined. The modification in calcium antagonist binding is functionally paralleled by an area specific increase in voltage-dependent calcium uptake. These data suggest that in hippocampus Substance P may be an endogenous regulator of voltage sensitive calcium channels.

Animals↗

Acute ethanol effect on calcium antagonist binding in rat brain.

We investigated the effect of acute ethanol administration on voltage-sensitive calcium channels (VSCC) by measuring [3H]nitrendipine ([3H]NTP) binding to crude synaptosomal membrane preparations from different rat brain areas, i.e. cerebral cortex, hippocampus and striatum. Ethanol enhances the number of binding sites shortly after the administration (40 min), then Bmax returns towards control values while the binding affinity increases. Kd decreased peaks 8 h after the oral administration and returns within the range of control values at 36 h. The in vitro addition of ethanol has no effect on [3H]NTP binding at various concentrations up to 600 mM. These results suggest that acute ethanol treatment modifies VSCC supporting the concept that the short-term neurochemical alterations induced by in vivo ethanol administration involve calcium channels.

Animals↗

Calmodulin content in human brain tumors.

Using a radioimmunoassay method, the particulate and soluble calmodulin levels were determined in biopsied specimens from normal human brain and from various human brain tumors. Both in normal and pathological tissues the major portion of calmodulin was revealed in the cytosol. The chromatographic elution profiles of calmodulin obtained from soluble and particulate fractions of the same specimen were identical, thus suggesting an identity of the supernatant and particulate form of calmodulin. In all the examined oncotypes, the calmodulin content was lower than in normal extracts and this biochemical feature could not have been correlated with the degree of malignancy of the neoplasia. Furthermore, the translocation of calmodulin from the particles to the cytoplasm, reported in other rapidly growing tumors, lacks in human cerebral ones. Our findings indicate that in human brain oncotypes the calmodulin distribution is quite different from that found in tumors taken from other tissues, where its level is increased and a positive correlation between calmodulin concentration and growth rate of neoplastic tissue has been revealed.

Adult↗

Alcohol impairs age-dependent adaptation of human lymphocyte beta-adrenergic receptors.

Lymphocyte beta-adrenergic receptor function and norepinephrine (NE) plasma concentration have been compared in normal subjects and in ethanol-addicted patients of different ages. Direct measurement of the density and properties of beta-adrenoceptors in membrane fractions was performed using the radioligand 125I-Iodocyanopindolol (ICYP). In normal subjects beta-receptor density decreased and norepinephrine plasma concentration increased with age. There was a statistically significant negative correlation between plasma norepinephrine and beta-receptor number. In ethanol-addicted patients the age-related modification in beta-receptor number and the correlation between plasma norepinephrine and beta-receptor density were lost, in spite of the fact that the increase of NE plasma concentration was still present. The ethanol-induced effects in lymphocyte beta-receptor may have consequences on immunological function and may be qualitatively similar to alterations in other tissues not routinely accessible in humans.

Adaptation, Physiological↗