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G Zsilla

Publications and source records attributed to G Zsilla.

18 recordsLinked to original sources
PubMed1995

Subtype-specificity of the presynaptic alpha 2-adrenoceptors modulating hippocampal norepinephrine release in rat.

In vivo brain microdialysis and high-performance liquid chromatography with electrochemical detection were used to study the effect of different selective alpha 2-antagonists on hippocampal norepinephrine (NE) release in freely moving awake rat. Systemic administration (0.5 mg/kg i.p.) of either the alpha 2AD-antagonist BRL 44408 or the alpha 2BC-antagonist ARC 239 did not significantly change the basal release of NE. At a higher dose (5 mg/kg i.p.) ARC 239 was still ineffective, whereas BRL 4408 caused a significant increase of the extracellular level of NF. Similar results were obtained from in vitro perfusion experiments. Rat hippocampal slices were loaded with [3H]NE and the electrical stimulation-evoked release of [3H]NE was determined. The alpha 2-antagonists were applied in a concentration range of 10(-8) to 10(-6) M, ARC 239 was ineffective, whereas BRL 44408 significantly increased the electrically induced release of [3H]NE. In agreement with the data of microdialysis and perfusion experiments, BRL 44408 displaced [3H]yohimbine from hippocampal and cortical membranes of rat brain with high affinity whereas ARC 239 was less effective. The pKi values of eight different alpha 2-adrenergic compounds showed a very good correlation (r = 0.98, slope = 1.11 P < 0.0001) in hippocampus and frontal cortex have the alpha 2-adrenoceptors have been characterized as alpha 2d-subtype. Our data indicate that hippocampal NE release in rat is regulated by alpha 2D-adrenoceptors, a species variation of the human alpha 2A-subtype.

Animals↗
PubMed1994

Differential changes in presynaptic modulation of transmitter release during aging.

The purpose of this study was to assess the functional role of presynaptic alpha 2-autoreceptors in noradrenergic transmission in the hippocampus and dopamine-2 heteroreceptors in cholinergic transmission in the striatum in young, adult, and senescent rats. Male and female Wistar rats (4, 12, and 24 months old) were used and the release of radioactivity from striatal and hippocampal slices that had been loaded either with [3H]choline or with [3H]norepinephrine was measured at rest and in response to field stimulation (2 Hz, 360 shocks). The release was challenged by sulpiride, a selective dopamine-2 receptor antagonist, and CH-38083, a selective alpha 2-adrenoceptor antagonist. The dissociation constant and the number of alpha 2-adrenoceptors was also determined by binding studies using [3H]yohimbine as ligand in crude membrane preparations of frontal cortex. There were an age-related changes in alpha 2-adrenoceptor-mediated negative feedback modulation of norepinephrine release and in the density and dissociation constant of alpha 2-adrenoceptors. They were reduced in senescent rats. In contrast the presynaptic modulation of striatal cholinergic transmission by dopamine-2 receptors was not altered during aging, but the storage capacity of and the release of acetylcholine from cholinergic interneurons was significantly lower.

Acetylcholine↗
PubMed1983

(-)-Deprenyl a selective MAO "B' inhibitor, increases [3H]imipramine binding and decreases beta-adrenergic receptor function.

In rats, a selective inhibition for 3 weeks of monoamineoxydase (MAO) type B elicited by daily doses of pargyline (2.5 mumol/kg) or (-)-deprenyl (1 mumol/kg) attenuated the NE dependent stimulation of cortical adenylate cyclase and reduced the number of brain recognition sites for beta-adrenergic receptor ligands. Similar actions were not elicited by a comparable dose regimen of (+)-amphetamine. Hence the inhibition of MAO B mimicks responses that are typically elicited by antidepressants. The molecular nature of the mechanisms involved cannot be understood, however, these mechanisms may not be identical for pargyline and (-)-deprenyl because this drug but not pargyline increased the number of [3H]imipramine recognition sites. Even high daily doses of pargyline (100 mumol/kg, for 3 weeks) failed to change [3H]imipramine binding though they still down regulated beta-adrenergic recognition sites, the NE stimulation of adenylate cyclase and the Bmax of [3H]mianserin and [3H]spiroperidol binding.

Animals↗
PubMed1981

Evidence of the modulatory role of serotonin in acetylcholine release from striatal interneurons.

The release of acetylcholine was studied in isolated striatal slices of the rat. The spontaneous and ouabain-stimulated release of acetylcholine was higher in those slices where serotonergic input was somehow impaired: raphe nuclei lesion or p-chlorophenylalanine pretreatment or 5, 7-dihydroxytryptamine pretreatment resulted in a higher release. L-(m-chlorophenyl)-piperazine, a pure serotonin receptor stimulant and D-fenfluramine, a serotonin releaser significantly reduced the release of acetylcholine evoked by ouabain. Serotonin antagonists (cyproheptadine, mianserine and methysergide) prevented the effect of serotonin agonists. When the serotonergic neurons were destroyed either by p-chlorophenylalanine or by 5, 7-dihydroxytryptamine pretreatment D-fenfluramine had no inhibitory action; however, the effect of L-(m-chlorophenyl)-piperazine was not affected. It is suggested that there is a link between serotonergic and cholinergic neurons in the striatum: serotonin released from raphe-striatal neurons is able to inhibit the release of acetylcholine from striatal interneurons.

Acetylcholine↗
PubMed1976

Regional changes in the rate of turnover of acetylcholine in rat brain following diazepam or muscimol.

Muscimol (8.8 mumol/kg i.v.) and diazepam (7.04 mumol/kg i.p.) decreased the rate of turnover of acetylcholine in midbrain and cortex of rat brain but failed to change acetylcholine turnover in striatum and hippocampus. The similarity in the profile of the action of diazepam and muscimol on acetylcholine turnover in various brain structures adds support to the view that GABA participates in mediating the actions of diazepam. Since the striatum contains an abundance of GABA neurones and intrinsic cholinergic neurones, it is inferred that the metabolism of acetylcholine, and presumably the activity of striatal cholinergic neurones are not regulated by the activation of GABA receptors. Similar considerations apply to the cholinergic pathway projecting from the septum to the hippocampus.

Acetylcholine↗
PubMed1976

Correlation between analgesia and the decrease of acetylcholine turnover rate in cortex and hippocampus elicited by morphine, meperidine, viminol R2 and azidomorphine.

In rats, an ED50 for analgesia of morphine, meperidine, viminol R2 or azidomorphine decreases the turnover rate of acetylcholine (TRACh) in cortex and hippocampus. These four analgetics fail to change to TRACh in striatum when given in a dose range from ED30 for analgesia up to a cataleptic dose. Viminol S2, a nonanalgesic stereoisomer of vimonol R2, fails to decrease the TRACh in cortex and hippocampus. Naltrexone, an opiate antagonist, also fails to change the cortical and hippocampal TRACh but it antagonizes the decrease in cortical and hippocampal TRACh elicited by the four analgetics. Since the ED50 of these four analgetics fails to change the TRACh in striatum which contains a high density of opiate receptors and intrinsic cholinergic neurons, but decreases the TRACh in hippocampus and cortex which contain a low density of opiate receptors, it can be inferred that opiate receptors are not exclusively involved in the regulation of TRACh. However, the results suggest that certain cholinergic pathways participate in the mediation of analgesia.

Acetylcholine↗
PubMed1975

The metabolism of azidomorphine in the rat.

The metabolism of [7,8-3H]azidomorphine and the in vivo stability of the azidogroup in azidomorphine and 14-hydroxyazidomorphine was studied. Asidomorphine conjugates with glucuronic acid, and is N-demethylated by rat liver microsomes. Detection by means of infrared spectroscopy proved that the azidroup in azidomorphine and 14-hydroxyazidomorphine strongly resists biotransformation in the rat.

Animals↗
PubMedDate not supplied

The effect of repeated doses of (-) deprenyl on the dynamics of monoaminergic transmission. Comparison with clorgyline.

The action of clorgyline and (-)deprenyl on the dynamics of dopaminergic and serotonergic transmission in the rat brain was compared. It was found, that daily administration of 0.25 mg/kg sc clorgyline, a specific MAO A inhibitor, reduced the turnover rate of both dopamine and serotonin after two weeks of injections. The treatment for two or four weeks with 0.25 mg/kg sc (-)deprenyl, a specific MAO B inhibitor, enhanced the turnover rate of dopamine and the fractional rate constant of dopamine efflux, reflecting an increased utilization rate of this amine in the striatum. Beside the augmentation of the dopamine turnover rate, the dopaminergic tone was also elevated by the reduction of the dopamine uptake in the striatum. Two week injections with the same dose of (-)deprenyl did not change the dynamics of serotonergic transmission.

Animals↗