Plasticity of neuronal L-type calcium channels.
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Animals↗
Biomedical subjects
F Battaini
Publications and source records attributed to F Battaini.
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↗
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↗
[Vascular and neuronal mechanisms of calcium antagonists. Significance in neurological therapy].
Calcium-channel entry blockers are drugs with different chemical properties and a common pharmacological characteristic. Calcium is very important in many physiological mechanisms and could be involved in neuronal damage following cerebral ischemia. Thus, calcium-channel blockers agents could be of interest in medical treatment of cerebrovascular diseases, headache and subarachnoid hemorrhage. Calcium-channel blockers seem to have a direct protective role against neuronal ischemic damage and/or a direct action on cerebral vessels. Some clinical experiences have suggested a protective role of nimodipine in the prevention of ischemic complications related to cerebral vasospasm after subarachnoid hemorrhage.
Blood-Brain Barrier↗
Cyclic AMP-dependent protein phosphorylation is reduced in rat striatum after chronic ethanol treatment.
Endogenous protein phosphorylation by cyclic AMP-dependent protein kinase was found reduced in striatal membranes obtained from chronic ethanol-treated rats. Experiments using an exogenous substrate show that the decreased response is due to a deficiency in the phosphorylating activity of the cyclic AMP-dependent protein kinase and not to a lack of endogenous substrate for phosphorylation.
Alcoholism↗
Neurotensin effect on dopamine release and calcium transport in rat striatum: interactions with diphenylalkylamine calcium antagonists.
The release of dopamine was investigated in rat striatal slices exposed in vitro to neurotensin. This peptide increased basal and K+-evoked dopamine release. Moreover neurotensin antagonized the flunarizine-induced inhibition of K+-stimulated dopamine release. The K+-evoked 45Ca2+ accumulation was also inhibited by flunarizine. This effect was antagonized by neurotensin. The results suggest that dopamine release in rat striatum is regulated by different molecular events also of peptidergic nature having as possible mechanism of action an influence on calcium ion movements.
Animals↗
Age-related changes in neurotensin content and receptors in various rat brain areas.
Neurotensin immunoreactivity (NT-IR) is significantly reduced in striatum, nucleus accumbens and hippocampus but not in frontal cortex, hypothalamus and septum of 24-month-old male Sprague Dawley rats. Neurotensin binding in cortex, striatum, hypothalamus and hippocampus shows a rather uniform decline with age. The changes in NT-IR content in striatum and nucleus accumbens are of particular interest in view of the existence of a functional relationship between dopamine and neurotensin.
Aging↗
Age-dependent changes in the mechanisms regulating dopamine uptake in the central nervous system.
Na+-dependent binding of 3H-Cocaine is located on dopaminergic terminals and is related to the dopamine uptake system. Studies on senescent rats indicate a decrease in 3H-Cocaine binding density in the striatum. In the same tissue an increase in the Km for dopamine uptake is observed. These changes might be relevant in the age-dependent alterations in dopaminergic function.
Aging↗
Partial reversal of asymmetry in microvessel neurochemical changes after ischemia by corpus callosum section.
Common carotid occlusion in the rat significantly decreases the density of beta-adrenergic receptors in preparations of microvessels obtained from ipsilateral and contralateral cerebral cortices. The disruption of nerve pathways connecting the hemispheres (callosal transection) partially reverses the effect of common carotid occlusion on beta-adrenergic receptor density in capillaries of the contralateral cortex. In addition, the destruction of the central noradrenergic system by intraventricular injection of 6-hydroxydopamine abolishes the effect of ischemia on capillary beta-adrenergic receptor function in both hemispheres. The results suggest that beta-adrenergic receptors located on microvessels are partially regulated by neuronal pathways and that focal ischemia induces neurochemical and functional changes in remote areas of the brain.
Animals↗
Changes in the interaction between CNS cholinergic and dopaminergic neurons induced by L-alpha-glycerylphosphorylcholine, a cholinomimetic drug.
The present study investigates the cholinomimetic properties of the drug L-alpha-glycerylphosphorylcholine (alpha-GPC) at CNS level. Experiments using tritium labelled alpha-GPC indicate that the drug reaches the brain after i.p. and per os administration. In order to study the cholinomimetic properties of this drug an indirect functional index of cholinergic activation was used. In fact cholinergic agonists induce an activation of striatal dopaminergic output. alpha-GPC both i.p. and per os administered increased striatal dihydroxyphenylacetic acid (DOPAC) content. In addition, the in vitro K+ stimulated dopamine release was increased in rats treated in vivo with alpha-GPC. Since alpha-GPC has a weak displacing activity in QNB binding, the in vivo cholinergic activity might be due to the fact that this drug may increase the availability of choline for acetylcholine synthesis leading to increased acetylcholine production. This activity may be useful in those situations such as aging in which cholinergic activity is deficient.
Animals↗
Age-dependent increase in [3H]verapamil binding to rat cortical membranes.
[3H]Nitrendipine bound to cerebral cortex membranes is displaced more efficiently by verapamil in old rats (24 months old) compared to young ones (3 months old). In addition, [3H]verapamil binding was studied in detail in 3-, 12- and 24-month-old rats. Aging increases the Bmax of [3H]verapamil, leaving the affinity unchanged. These observations further indicate that aging may affect calcium channels leading to a derangement of calcium movements which in turn alter neuronal activity.
Age Factors↗
Age-related reduced affinity in [3H]nitrendipine labeling of brain voltage-dependent calcium channels.
Literature data indicate a reduced calcium uptake in synaptosomes prepared from old rat brains. On this line, the present paper investigates the binding of ([3H]NDP) to brain synaptic membranes prepared from rats at different ages from birth up to 24 months of age. The binding is undetectable at birth but reaches within 9-18 day the values observed in adults [3H]NDP binding affinity and sensitivity to calcium were decreased in old rats (24 months). Tritiated dihydropyridines are believed to label voltage-dependent calcium channels (VDC). The observed age-related reduction in binding suggests that the characteristics of VDC in the aged brain may change.
Age Factors↗
Ethanol administration in vivo alters calcium ions control in rat striatum.
The present paper investigates the effect of chronic ethanol treatment administered through drinking water on [3H]nitrendipine binding and 45Ca uptake in rat striatum. The calcium-independent [3H]nitrendipine binding was slightly increased in treated rats, while the calcium stimulation of the binding was reduced to one fifth of the controls. In striatal slices prepared from a similar group of ethanol-treated rats the K+-stimulated 45Ca uptake was greatly reduced. These results are the first evidence of calcium-antagonist binding-site 'plasticity' following an in vivo pharmacological manipulation correlated with a change in calcium ion transport. In addition, the effect of ethanol on calcium-entry regulation may be a mechanism important for the understanding of its neurotoxic action.
Animals↗
Differential sensitivity of [3H]nitrendipine binding to cations of toxicological interest in various rat brain areas.
[3H]Nitrendipine ([3H]NTP) is a radiolabelled calcium antagonist which can be used to study neuronal calcium (Ca2+) channels. The interaction of Mn2+, Zn2+, Pb2+ and La3+ on [3H]NTP binding was studied in 3 brain areas particularly rich in [3H]NTP binding sites. Differences were observed in the brain regional distribution of [3H]NTP binding as well as in their sensitivity to the metal ions Pb, Mn and Zn. The binding data suggest that neuronal Ca2+ channels in different brain areas display distinct sensitivity to selected divalent cations.
Animals↗
Kynurenine may directly interact with GABA receptors in rat brain.
Previous studies have shown that kynurenine may have convulsant activity. In the present investigation the intracerebroventricular injection of L- but not D-kynurenine induced convulsions in the rat. In vitro, L- but not D-kynurenine was able to displace 3H-GABA from rat brain membrane preparations. The action was specific for 3H-GABA and was not observed with other ligands. The data suggest that the convulsant activity of L-kynurenine might be due to an interaction with GABA receptors.
Animals↗