PubMed Health⌕ Search

Biomedical subjects

A Vaccari

Publications and source records attributed to A Vaccari.

At least 19 recordsLinked to original sources
PubMed1995

The tyramine-labelled vesicular transporter for dopamine: a putative target of pesticides and neurotoxins.

This study defined the ability of a large sample of heterogeneous pesticides and neurotoxins to interact with the [3H]tyramine-labelled vesicular transporter of dopamine in rat striatum. Botanical (with rotenone as the most potent), and organochlorine (Kepone) insecticides, as well as fungicides (Zineb), as a whole, consistently inhibited [3H]tyramine binding, with Ki values ranging from 5 nM to 10 microM. ATP/Mg(2+)-dependent [3H]tyramine uptake to purified striatal synaptic vesicles was also inhibited by rotenone. Organophosphate and carbamate insecticides, and miscellaneous herbicides poorly antagonized [3H]tyramine binding, yielding Ki values exceeding 10 microM. Several, though not all, of the best recognized central neurotoxins tested were major binding antagonists. Their rank order of potency was 1-methyl-4-phenylpyridinium ion (MPP+) > trimethyltin > or = 6-hydroxydopamine > N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) > 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with Ki values ranging from 35 nM to 3 microM. Overall, the potent interaction of selected pesticides and chemicals with the vesicular transporter for dopamine, although, by itself, not synonymous with neurotoxicity, would argue for a likely impairment of transmitter homeostasis, or the putative formation of neurodegenerative toxin pools.

Animals↗
PubMed1995

Poor interaction of some quinolizidine derivatives with dopamine D1- and D2- type receptors.

The displacement of [3H]SCH-23390 and of [3H]spiperone from striatal, dopamine D1- and D2-type receptors by several quinolizidinyl-derivatives of bi- and tricyclic systems was investigated. All tested compounds did not affect SCH-23390 binding and exhibited only weak activity on spiperone binding to D2 binding sites (Ki = 1.9 microM). Therefore the good deconditioning activity (CAR blockade in rats) of 6-chloro-1-lupinyl-3-methyl-quinoxalinone (18) must rely on interactions with other kinds of receptors.

Animals↗
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↗
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↗
PubMed1990

Dopaminergic dysfunction in neonatal hypothyroidism: differential effects of GM1 ganglioside.

The effects of daily treatment with GM1 ganglioside (30 mg/kg s.c.) from birth to day 30, on striatal pre- and postsynaptic markers of the dopaminergic system in euthyroid- and 32 day-old hypothyroid rats were studied. The purpose was to assess whether GM1 could prevent the extensive, hypothyroidism-provoked impairment of dopaminergic neurotransmission. Neonatal administration of GM1 well counteracted the hypothyroidism-related deficits in striatal synaptosomal uptake of [3H]dopamine and in membrane binding of [3H]tyramine, a putative marker for the vesicular carrier of dopamine. In the hypothyroid striatum, the decrease of concentrations of DOPAC and HVA, the loss of [3H]SCH-23,390-labelled D1-receptors and the decrease of basal- or dopamine-stimulated, D1-mediated activity of adenylate cyclase were not prevented by GM1. Although somatic and neurobehavioural aberrations of hypothyroids were not at all or only partially ameliorated, a slight improvement of the thyroid status was suggested by less decreased levels of serum thyroxine (T4) after treatment with GM1. The ganglioside-driven selective recovery of the transport and storage process of [3H]dopamine might result either from a chronically-exerted stimulation by GM1 on the NA/K- and Mg-ATPase activities, thus reflecting on the ATPase-dependent neuronal and vesicular transport processes of dopamine or from a GM1-promoted maturation of the otherwise retarded functionality of dopaminergic nerve endings in the neonatal hypothyroid striatum.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Neonatal hypothyroidism induces striatal dopaminergic dysfunction.

Oral administration of the antithyroid drug methimazole (50 mg/kg per day) to rats during the last six days of pregnancy, and subsequent daily s.c. injection of methimazole (20-30 mg/kg) to their pups from birth to postnatal day 30 provoked hormonal and somatic alterations resembling (with all caution to any association between rodent and human data) those of congenital hypothyroidism. The steady-state concentrations of striatal dopamine were similar in hypothyroid and euthyroid, 32-day-old rats, while the levels of the dopamine metabolites 3,4-dihydroxyphenylacetic and homovanillic acids were markedly decreased in hypothyroidism. The results of this and our earlier study [Vaccari A. and Gessa G. L. (1989) Neurochem. Res. 14, 949-955] show that the maximal synaptosomal uptake of [3H]dopamine, an index for the density of nigrostriatal dopaminergic terminals, and the maximum number of membrane [3H]tyramine binding sites, reflecting the concentration of the vesicular transporter for dopamine, were decreased in the hypothyroid striatum. There was also a loss of those D1-type dopaminergic receptors claimed to be located on neurons intrinsic to the striatum, and, consequently, dopamine-stimulated, D1-regulated adenylate cyclase activity was depressed. It is suggested that individual dopaminergic nerve endings in the neonatal hypothyroid striatum must contain more dopamine, owing to some loss of pertinent innervation and, therefore, to the presence of less vesicular transport sites for dopamine. Hypothyroidism-related decreases in the maximum number of striatal D1- and, reportedly, D2-receptors, plus the impairment of D1-coupled second messenger activity, may play a role in the derangement of those neurobehavioural patterns where a dopaminergic regulation is putatively implied.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1990

Effects of neonatal and adult thyroid dysfunction on thymic oxytocin.

Prenatal plus neonatal administration of methimazole (MMI), a procedure provoking marked hypothyroidism in rats, increased by about 100% the thymic content of oxytocin and severely (by approximately 80%) decreased the thymus weight, compared to euthyroid counterparts. Adult-onset, propylthiouracyl (PTU)-induced hypothyroidism, while provoking thymic involution, or thyroxine (T4) hyperthyroidism, did not affect oxytocin concentrations. Thymic involution and increases in thymus oxytoxin could also be obtained with repeated administration of the potent glucocorticoid dexamethasone. However, since corticosterone, unless subchronically injected at largely supraphysiological doses, was previously shown to have no influence on thymic parameters of young adult rats, a major involvement of the neonatal adrenal axis in oxytocin alterations could be excluded. It is suggested that the ontogenesis of thymic oxytocin production is under thyroid control.

Aging↗
PubMed1989

[3H]tyramine binding: a comparison with neuronal [3H]dopamine uptake and [3H]mazindol binding processes.

[3H]Spiperone [( 3H]SPI) binding sites in rat or bovine striata have been solubilized using CHAPS or digitonin detergents. Solubilized sites retained the binding characteristics of those in native membrane preparations. The same solubilized material, however, did not bind [3H]tyramine [( 3H]PTA), thus indicating that [3H]PTA binding sites and DA receptors are different chemico-physical entities. In membrane preparations or crude synaptosomes obtained from the c.striatum of neonatally-rendered hypothyroid rats, when central DA-pathways are impaired, both [3H]PTA binding and [3H]DA uptake processes were markedly decreased, with no effect on [3H]mazindol [( 3H]MAZ) binding, compared to euthyroids. Reserpine, a well-known inhibitor of DA-uptake into a variety of secretory vesicles, and a potent in vivo and in vitro inhibitor of [3H]PTA binding, did not affect the [3H]MAZ binding process. This further supported the suggestion that while [3H]PTA binding sites are almost totally associated with the vesicular transporter for DA, [3H]MAZ does label a site involved in the DA-translocation across the neuronal membrane. The latter process seems to be rather insensitive to thyroid hypofunction, when however the intracellular storage of DA might be consistently impaired. In conclusion, PTA might be well exploited as a marker of the DA vesicular transporter through its molecular characterization, whenever possible.

Animals↗
PubMed1989

Simple and complex dislocations of the carpus.

The authors report 33 dislocations of the carpus; 9 simple lunate dislocations and 24 complex fracture dislocations. The number and variety of the lesions and, in particular, the variety of the types of treatment carried out allow us to draw several conclusions regarding the correct management of these rare lesions based on a long-term evaluation of the results.

Adolescent↗
PubMed1986

High affinity binding of [3H]-tyramine in the central nervous system.

Optimum assay conditions for the association of [3H]-para-tyramine [( 3H]-pTA) with rat brain membranes were characterized, and a saturable, reversible, drug-specific, and high affinity binding mechanism for this trace amine was revealed. The binding capacity (Bmax) for [3H]-pTA in the corpus striatum was approximately 30 times higher than that in the cerebellum, with similar dissociation constants (KD). The binding process of [3H]-pTA involved the dopamine system, inasmuch as (a) highest binding capacity was associated with dopamine-rich regions; (b) dopamine and pTA equally displaced specifically bound [3H]-pTA; (c) there was a severe loss in striatal binding capacity for [3H]-pTA and, reportedly, for [3H]-dopamine, following unilateral nigrostriatal lesion; (d) acute in vivo reserpine treatment markedly decreased the density of [3H]-pTA and, reportedly, of [3H]-dopamine binding sites. In competition experiments [3H]-pTA binding sites, though displaying nanomolar affinity for dopamine, revealed micromolar affinities for the dopamine agonists apomorphine and pergolide, and for several dopamine antagonists, while having very high affinity for reserpine, a marker for the catecholamine transporter in synaptic vesicles. The binding process of [3H]-pTA was both energy-dependent (ouabain-sensitive), and ATP-Mg2+-insensitive; furthermore, the potencies of various drugs in competing for [3H]-pTA binding to rat striatal membranes correlated well (r = 0.96) with their reported potencies in inhibiting [3H]-dopamine uptake into striatal synaptosomes. It is concluded that [3H]-pTA binds at a site located on/within synaptic vesicles where it is involved in the transport mechanism of dopamine.

Animals↗
PubMed1985

Selective effects of thiol reagents on the binding sites for imipramine and neurotransmitter amines in the rat brain.

The action of the antithyroid drugs methimazole (MMI) and propylthiouracil (PTU) on the binding of [3H]-imipramine, [3H]-5-hydroxytryptamine [3H]-5-HT) (to 5-HT1-receptors) and [3H]-spiperone (to 5-HT2-, D2-receptors) of rat brain membranes has been examined. The synaptosomal uptake of [3H]-5-HT was also studied. Micromolar concentrations of the disulphide bond reducing agents MMI, PTU, dithiothreitol (DTT) and mercaptoethanol increased both the binding of [3H]-imipramine and the uptake of [3H]-5-HT. In contrast, they decreased the number of 5-HT1-receptors, and did not affect 5-HT2-and D2-sites. Reaction with membrane-bound sulphydryl (SH) groups by micromolar concentrations of N-ethylmaleimide (NEM), hydroxymercuribenzoic acid (PCMB), or Ellman's reagent (DTNB) decreased the binding of [3H]-imipramine, the number of 5-HT1-receptors, and the uptake of [3H]-5-HT. Millimolar concentrations of NEM were necessary in order to decrease partially 5-HT2- and D2-receptors. The effects of NEM on imipramine recognition sites and on the uptake of 5-HT could be prevented by DTT; protection was not obtained in other receptor systems. Three groups of receptors have been, thus, postulated, based upon their different sensitivity towards alterations in membrane [disulphide bridges in equilibrium SH] equilibrium: Group I, including imipramine recognition sites and the uptake system for 5-HT; Group II, including 5-HT1-receptors; Group III, including 5-HT2-and D2-receptors.

Animals↗
PubMed1985

Effects of neonatal antithyroid treatment on brain [3H]-imipramine binding sites.

The action of the antithyroid, sulphydryl reagent methimazole (MMI) on the specific binding of [3H]-imipramine in the cerebral cortex and corpus striatum of immature and mature rats has been examined. Chronic administration of MMI through the first 30 days of life decreased the number of imipramine binding sites in cortical but not striatal membranes, as assessed 48 h after the last injection of goitrogen. A similar treatment did not affect the binding profile of [3H]-imipramine in mature rats. Acute administration of MMI to 30 day-old rats increased the number of imipramine binding sites shortly after the injection, an effect no longer evident 48 h later. MMI in vitro increased the binding of [3H]-imipramine. It is concluded that maturational impairment of the hypothyroid cortex, rather than any alteration of membrane bound thiol groups, was a major cause for the diminished binding of [3H]-imipramine in MMI-treated, immature rats.

Aging↗
PubMed1985

Transposition of the 5th to the 4th ray by osteotomy of the hamate.

The authors present 5 cases of transposition of the 5th to the 4th ray according to Le Viet's method. This is indicated for the aesthetic and functional defects that follow total or subtotal amputation of the ring finger. The technique consists of radial transposition of the whole ray and intracarpal arthrodesis after cuneiform osteotomy of the hamate bone. It is easier to perform than the traditional metacarpal osteotomy and the results were uniformly good.

Adult↗
PubMed1984

[Cigarette smoking. A pilot project of dehabituation and experimental research].

An interdisciplinary approach was adopted in a pilot programme research project as the most effective way to obtain concrete results in curing tobacco-addiction. The various stages and effects of the treatment are analysed as a means of identifying the most appropriate techniques. The early results are reported under separate headings according to treatment type (psychological, neurophysiological, dietary, clinical, chemical).

Adult↗
PubMed1983

Effects of neonatal dysthyroidism on serotonin type 1 and type 2 receptors in rat brain.

Long-Evans, male and female rats born of mothers kept on an iodide-rich diet prior to delivery and during lactation, were fed this diet after weaning, thus becoming slightly hypothyroid. A more severe hypothyroidism was also provoked with the chronic administration of methimazole to Long-Evans iodide-supplemented, or Charles River iodine-deprived pups through the first month of age. Additional Long-Evans rats were made hyperthyroid with a daily injection of triiodothyronine (T3) through the first 29 days of age. Severe hypothyroidism in both strains of rats markedly increased the density of serotonin type 1 (5-HT1) and type 2 (5-HT2) receptors in the brain (less cerebellum, corpus striatum and olfactory bulbs) at 31-32 days of age. Receptor alterations were not correlated to either the rise in thyrotropin (TSH) levels in hypothyroidism or the direct influence of residual methimazole after the last treatment, or to neonatal malnutrition. This increase in 5-HT receptor density might represent an adaptive (supersensitivity) postsynaptic response to the state of central serotonergic hypofunction occurring in hypothyroidism. Though receptor alterations might be important, their precise functional role in the etiogenesis of hypothyroid-associated mental disturbances is difficult to ascertain.

Animals↗