Biomedical subjects
Publications and source records attributed to S Govoni.
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.
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.
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.
[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.
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.
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.
Cerebral capillary endothelium forms a barrier limiting and controlling the movement of ions and solutes between blood and brain. Recent anatomical, physiological and biochemical studies have suggested the possibility that capillary function may be directly controlled by neuronal structures. Alterations in neuronal systems involved in the regulation of microcirculation may account for microvascular dysfunctions which occur in different pathologic conditions.
The effect of various Calcium Entry Blockers (CEBs; nifedipine, flunarizine, diltiazem, verapamil) on ethanol-induced bronchoconstriction was studied in normal healthy volunteers. Nifedipine and diltiazem inhibited the bronchoconstriction and verapamil and flunarizine had no effect. The data favour the general hypothesis of differential tissue sensitivity to the various CEBs. The activity of CEBs on bronchomotor tone may be of therapeutic value in patients in whom bronchodilator activity is recommended in addition to the cardiovascular action.
Four neuropeptides (substance P, methionine-enkephalin, neurotensin and cholecystokinin) were measured by radioimmunoassays in a number of brain regions of deceased patients with mental illnesses and controls. The most striking finding in these studies was that methionine-enkephalin concentrations in caudate nuclei of chronic paranoid schizophrenic patients were reduced relative to several control groups. Neuroleptics had no obvious effects on any of the four measured neuropeptides. These findings are not inconsistent with the hypothesis that methionine-enkephalin may be involved in some of the pathology of the schizophrenic syndrome.
[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.
Active uptake of 3,4-dihydroxyphenylethylamine (dopamine) is sodium- and temperature-dependent, strongly inhibited by benztropine and nomifensine, and present in corpus striatum and nucleus accumbens. In rat striatum dopamine uptake is related to a receptor that is specifically labelled by [3H]cocaine in the presence of Na+ and is located on dopaminergic terminals. The dopamine uptake is differentially affected in the two areas by single or repeated injections of cocaine. Cocaine inhibits dopamine uptake in slices of corpus striatum. Moreover Na+-dependent [3H]cocaine binding is not detectable in nucleus accumbens. Nomifensine inhibits [3H]dopamine uptake by interacting with low- and high-affinity sites in corpus striatum, but shows only low affinity for dopamine uptake in nucleus accumbens. The present data indicate that different mechanisms are involved in the regulation of dopamine uptake in corpus striatum and nucleus accumbens.
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.
Calcium entry blocker (CEB) use has been proposed in a variety of neurological dysfunctions. Some of the new clinical applications suggest a direct non-vascular action on neuronal activity. This view is supported by the observation that in brain CEBs bind preferentially to neuronal terminals and not to vascular elements. The data reported indicate that CEBs modify both in vitro and in vivo neurotransmitter release using brain slices and that their binding sites display some degree of plasticity in various experimental conditions altering neuronal transmission.
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Plasma Cortisol and Beta-Endorphin/Beta-Lipotropin-immunoreactivity concentrations were measured in 51 healthy aged subjects. A direct correlation was found between the plasma concentrations of the two hormones. The data suggest that beta-endorphin/beta-lipotropin is not only released during stress but also in resting conditions.
The effect of lead as a neurotoxic agent has been associated with alterations in calcium metabolism. On this line, the present study shows that lead alters the characteristics of [3H]nitrendipine ([ 3H]NDP) binding to rat striatal membranes. In vitro, lead shares the action of calcium in enhancing [3H]NDP binding although it is more potent on a molar basis. In vivo, lead exposure through drinking water enhances [3H]NDP binding to crude synaptosomal membrane preparations. This effect is lost when membranes are washed with EDTA-EGTA, indicating that the increased binding is due to the persistence of lead in the brain of treated rats.
Recent progress in the field of neurochemical and neuropharmacological research into food intake control by the central nervous system is discussed. Particular emphasis is laid on the fundamental role played by the hypothalamus as the integration centre for the various afferent impulses and the processor of behavioural patterns aimed at the quest for, and ingestion of food. Physiopathological knowledge of central appetite regulation mechanisms is essential for the understanding of the aetiopathogenesis of many clinical forms of human obesity and is the best basis for decisions on the pharmacological and behavioural approach to the treatment of this disease.
The basal release of Met-enkephalin immunoreactive material (ME-IR) from rat striatal slices is doubled by the in vitro addition of 5 X 10(-5) M dopamine. The K+ evoked release of ME-IR is also slightly enhanced by exposing the slices to dopamine. The effect of dopamine is shared by apomorphine but not by norepinephrine. Neuroleptics do not alter the basal or the K+-stimulated ME-IR release but reverse the dopamine-induced increase. These results suggest that the stimulation of dopamine receptors may influence the enkephalin release within striatum.