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Biomedical subjects

T Bartfai

Publications and source records attributed to T Bartfai.

At least 199 records · Page 11Linked to original sources
PubMed1986

Intracellular injection of cGMP-dependent protein kinase results in increased input resistance in neurons of the mammalian motor cortex.

Purified, cyclic GMP-dependent protein kinase (cGPK) was pressure-injected into neurons of the precruciate cortex of awake cats. Input resistances increased within seconds after injection and remained elevated for 2 min or longer. The increases were larger when cGPK was injected in a mixture with 10 microM cGMP than when injected alone. Injections of heat-inactivated cGPK, with or without 10 microM cGMP, failed to produce increases in input resistance. The present results indicate that injection of activated cGPK into neurons of the mammalian motor cortex can mimic actions of extracellularly applied acetylcholine and intracellularly applied cGMP, the latter in 100-fold higher concentrations than those used here, in neurons of the same cortical areas.

Action Potentials↗
PubMed1986

Efflux of cyclic guanosine 3',5'-monophosphate from cerebellar slices stimulated by L-glutamate or high K+ or N-methyl-N'-nitro-N-nitrosoguanidine.

The efflux of cyclic guanosine 3',5'-monophosphate (cGMP) was studied from rat cerebellar slices which were stimulated by L-glutamate (1 mM), or by depolarizing concentrations of K+ (60 mM) or by the nitroso compound, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Via different mechanisms these agents stimulated cGMP synthesis producing several fold elevation of the cGMP content of the tissue slices. Simultaneously with the elevation of the intracellular (intra slice) concentrations of cGMP, a temperature-and time-dependent efflux of cGMP into the medium took place. This efflux was maximal at 5 min and could be inhibited by the known inhibitor of anion transport, probenecid, in a concentration-dependent manner. The results suggest the presence of an efflux system for cGMP, which may participate together with the well-characterized 3',5'-cyclic nucleotide phosphodiesterases in reduction of elevated cGMP levels.

Animals↗
PubMed1986

Serotonin type-2 receptor mediated regulation of substance P release in the ventral spinal cord and the effects of chronic antidepressant treatment.

Regulation of the release of substance P (SP) by the coexisting neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in the ventral spinal cord and the effects of chronic antidepressant treatment mediated changes in serotonin metabolism on the regulation, were examined. The K+ (40 mmol/l) evoked release of (SP) from slices of the ventral spinal cord of the rat was potentiated by (5-HT) applied to 100 mumol/l concentration. This effect was blocked by the serotoninergic antagonists methysergide (10 mumol/l), methiotepin (10 mumol/l) and fully blocked by ketanserin (10 mumol/l). Thus the 5-HT receptor which regulates the release of SP appears to belong to the type-2 5-HT receptors. Chronic treatment with the selective serotonin uptake inhibitor zimelidine (14 days, 2 X 10 mumol/kg/day, p.o.) lowered the tissue levels of the 5-HT metabolite: 5-hydroxyindol acetic acid (5-HIAA) and elevated the tissue levels of SP in both the ventral and dorsal spinal cord as compared to that in the vehicle treated group (14 days, 2 X 5 ml saline/kg/day, p.o.). The decrease in the 5-HIAA levels after chronic zimelidine treatment was quantitatively similar in the dorsal (33%, p less than 0.01) and ventral (31%, p less than 0.05) spinal cord. The increase in SP levels after chronic zimelidine treatment was more pronounced in the ventral cord (80%, p less than 0.01) where the majority of the SP containing nerve endings also contain 5-HT, than in the dorsal spinal cord (22% increase in SP, p less than 0.05), where only a minor fraction of the SP-containing nerve endings shows a 5-HT/SP coexistence.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Multiple biochemical deficits in both gray and white matter of Alzheimer brains.

A biochemical investigation of 21 brains from patients with dementia of Alzheimer type (AD/SDAT) and 22 brains from controls was made. In the normal brains 5-hydroxytryptamine (5-HT), noradrenaline (NA) and dopamine (DA) were reduced with age while their metabolites were not reduced. In the brains from the Alzheimer patients the examination of gray matter (caudate nucleus and hippocampus) showed a significant reduced activity of choline-acetyl transferase (CAT) and a reduction of acetylcholinesterase (AChE) that bordered significance in the hippocampus. In the brains from the Alzheimer patients a disturbance was found in the 5-HT system in the form of reduced levels of 5-HT and 5-hydroxyindolacetic acid (5-HIAA). The catecholamine systems were also disturbed but to a less extent. In the 5-HT and DA systems the active amines as well as the metabolites were reduced in the brains from patients with AD/SDAT indicating not only a possible neuronal loss but also an incapacity of the remaining neurons to compensate for the loss by an increased turnover. The lipid content was slightly reduced in gray matter of the demented brains. In white matter there was a more severe reduction of the lipids and in this tissue also the cerebrosides and sulfatides were reduced. It is concluded that in brains from patients with AD/SDAT there are multiple biochemical deficits in gray as well as in white matter. The changes in white matter may be of pathogenetic importance in subgroups of AD/SDAT.

Age Factors↗
PubMed1986

Dopamine release is enhanced while acetylcholine release is inhibited by nimodipine (Bay e 9736).

The calcium-channel ligand, nimodipine (Bay e 9736), in submicromolar concentrations (10(-7) to 10(-5) M), enhanced the potassium (25 mM) or electrical stimulation (1 Hz, 1 ms, 180 pulses) evoked release or [3H]dopamine from rat striatal slices, while it inhibited the release of [3H]acetylcholine. Nimodipine had similar effects on slices from the cerebral cortex loaded with [3H]dopamine or [3H]acetylcholine, the electrical stimulation evoked release of the catecholamine was enhanced, while release of [3H]acetylcholine was suppressed. The data indicate that nimodipine may distinguish between Ca2+ channels in dopaminergic and cholinergic nerve-terminals. The simultaneous elevation of dopamine release and suppression of acetylcholine release may prove useful in the treatment of Parkinson's disease.

Acetylcholine↗
PubMed1986

Effects of chloride ion substitution on the frequency dependence and alpha-autoinhibition of [3H]noradrenaline secretion in guinea-pig vas deferens.

Guinea-pig isolated vas deferens, in which the stores of noradrenaline (NA) had been labelled by preincubation with [3H]NA, was used to study the effects of substitution of chloride with other anions, on transmitter secretion evoked by electrical stimulation of postganglionic sympathetic nerves. Chloride was omitted from the Tyrode's solution and substituted with acetate, nitrate, methylsulphate, sulphate or HEPES. All substituents increased both the spontaneous and the stimulus-evoked fractional secretion of [3H]NA under control conditions. The effect was essentially the same at all frequencies of stimulation (1-8 Hz). In the presence of the alpha-adrenoceptor blocker phentolamine, which enhanced the secretion of [3H]NA in all media, the secretion was not further enhanced by chloride substitution. Chloride substitution reduced the depressing effect of exogenous NA on the secretory response. In conclusion, chloride ions may be required for full expression of alpha-adrenoceptor-mediated inhibition of [3H]NA secretion, but do not markedly influence facilitation by increased frequency of stimulation.

Animals↗
PubMed1986

Prevention by nimodipine, a calcium entry blocker, of the effect of alpha 2-adrenoceptor blocking agents on noradrenaline release: differential effects of nimodipine, on [3H]noradrenaline and [14C]acetylcholine release measured concomitantly from the guinea-pig ileum.

The calcium channel blocker, nimodipine (Bay e 9736), inhibited the evoked (1 Hz, 1 msec, 180 pulses) release of [14C]acetylcholine ([14C]ACh) while it enhanced the release of [3H]noradrenaline ([3H]NA) measured concomitantly from the same longitudinal muscle strip of guinea-pig ileum loaded with [14C]choline and [3H]noradrenaline. These effects of nimodipine were concentration-dependent: in 0.1 microM concentration yielding maximal inhibition of [14C]ACh release and in 0.5 microM concentration yielding half maximal stimulation of [3H]NA-release. Enhancement of [3H]NA-release by nimodipine was strongly dependent on stimulation frequency while the inhibitory effect of nimodipine on release of [14C]ACh did not depend on stimulation frequency in the 0.5-10 Hz range. In addition, in the presence of nimodipine when the release of [3H]NA was enhanced, i.e. when a significant negative feedback operation could have been expected, alpha 2-adrenoceptor blocking agents (yohimbine and idazoxane) failed to enhance [3H]NA-release. It is proposed that nimodipine somehow exerts a presynaptic alpha 2-adrenoceptor blocking property at noradrenergic axon terminals through an effect on calcium entry, which may be an essential step in events linking alpha 2-adrenoceptor activation and inhibition of noradrenaline release.

Acetylcholine↗
PubMed1985

Anticholinergic potency of psychoactive drugs in human and rat cerebral cortex and striatum.

The affinity of selected antipsychotic and antidepressant drugs for the muscarinic receptor was studied in membranes from both human and rat striatum and cerebral cortex. While there are regional differences in the anticholinergic potency of the drugs, there is good agreement between the obtained inhibition constants from the corresponding human and rat striatum (r: 0.98) and from human and rat cerebral cortex (r: 0.96). There is also good agreement between the obtained Ki values within one species: human cerebral cortex versus human striatum (r: 0.99) and for rat cerebral cortex and rat striatum (r: 0.87). Thus, the previously published quantitative estimates of the antimuscarinic activity of psychoactive drugs which were derived from studies on membranes from rat brain give an accurate estimate of the antimuscarinic activity in human brain. The drugs tested in this study include chlorpromazine acetophenazine, haloperidol, sulpiride, remoxipride (FLA-731 (-), a substituted benzamide), amitriptyline and two serotonin uptake blockers: norzimelidine and alaproclate.

Aged↗
PubMed1985

Serotonergic potentiation of muscarinic agonist evoked tremor and salivation in rat and mouse.

The dose-effect of oxotremorine upon the onset, duration and magnitude of tremor and salivation was studied in both mice and rats. The threshold doses of oxotremorine (SC) for eliciting tremor were above 50 micrograms/kg in mice and above 150 micrograms/kg in rats and the threshold doses for eliciting salivation were above 75 micrograms/kg in mice and above 200 micrograms/kg in rats. Alaproclate, a nontricyclic 5-HT uptake inhibitor, when injected 30 min prior to the administration of the cholinergic agonist, produced a dose-dependent enhancement of tremor and salivation in both rats and mice. Alaproclate itself did not produce these effects in the absence of a muscarinic cholinergic stimulant such as oxotremorine, arecoline or the acetylcholine esterase inhibitor physostigmine. Both salivation and tremor could be fully blocked by atropine at any dose of the cholinergic stimulant and of alaproclate used. The potentiating effects of alaproclate on salivation and tremor could also be blocked by two serotonin receptor antagonists, metitepine and danitracen, but not by metergoline or cinanserin. Other compounds which inhibit the uptake of 5-HT such as fluoxetine, citalopram, norzimeldine, zimeldine and the non-tricyclic antidepressant, iprindol, did not enhance the cholinergic agonist induced tremor or salivation under the same conditions as did alaproclate. It is suggested that alaproclate exerts the potentiating effect at a hitherto undefined serotonergic receptor site.

Alanine↗
PubMed1985

In vivo and in vitro studies on the potentiation of muscarinic receptor stimulation by alaproclate, a selective 5-HT uptake blocker.

Alaproclate (10-60 mg/kg) injected i.p. into male mice potentiated and prolonged the oxotremorine and physostigmine-induced tremor in a dose-dependent manner. Atropine completely blocked the tremor caused by oxotremorine or physostigmine both in the presence and absence of alaproclate. Pretreatment with the 5-HT receptor antagonist metitepine completely blocked the enhancement of oxotremorine-induced tremor caused by alaproclate. Biochemical studies indicated that the above effects cannot be explained by assuming that alaproclate a) acts as a cholinergic agonist, b) inhibits the acetylcholine esterase, c) interferes with choline uptake or acetylcholine synthesis, or d) directly potentiates the release of acetylcholine. In ligand binding studies alaproclate was found to be a weak competitive inhibitor of muscarinic antagonist binding to membranes from the rat cerebral cortex, rat striatum, human cerebral cortex and human striatum. (Ki approximately 28-40 microM in all four tissues). The present results suggest that alaproclate may potentiate muscarinic responses by a mechanism involving serotonergic receptor mechanisms rather than by a direct interaction with the muscarinic cholinergic receptors.

Alanine↗
PubMed1984

Neuropeptide Y receptor in the rat brain.

The specific binding of the chloramine-T iodinated neuropeptide Y (125I-NPY) to membranes from rat cerebral cortex was investigated using equilibrium binding and kinetic methods. The equilibrium binding of 125I-NPY at 37 degrees C was characterized by a Kd value of 0.38 nM. The receptor densities in the cerebral cortex, hypothalamus and cerebellum were 0.45 pmol/mg, 0.47 pmol/mg and 0.04 pmol/mg protein respectively. The binding site for 125I-NPY was sensitive to treatment with proteolytic enzymes and thiol reagents. The binding showed a sharp optimum at pH 7-7.7 and was inhibited by increasing concentrations of Mg2+.

Animals↗
PubMed1984

Regulation of neuropeptide Y (NPY) binding by guanine nucleotides in the rat cerebral cortex.

In the presence of GTP, GDP, GMPP(NH)P, GMPP(CH2)P, GMPP(S)P but not in the presence of GMP, cGMP or ATP, the high affinity binding of neuropeptide Y (NPY) was reduced in a dose-dependent manner. GTP (0.1 mM) diminished the maximal binding capacity for 125I-labelled NPY by 40% without any change in the equilibrium dissociation constant of the receptor 125I-labelled NPY complex.

Adenine Nucleotides↗
PubMed1984

Uncoupler-accelerated efflux of 5-hydroxytryptamine from platelets of healthy subjects and patients with unipolar and bipolar depression.

The efflux of 14C-5-hydroxytryptamine (5HT) from platelets of 25 depressed patients (16 unipolar and 9 bipolar) and 22 control subjects was studied in the presence of carbamyl cyanide m-chlorophenylhydrazone (FCCP), which dissipates H+ gradients. FCCP (0.31 microM), at 10 minutes' incubation time, enhanced the efflux of 14C-5HT to a significantly higher extent from platelets of patients with bipolar depression than from platelets of control subjects. An analysis of variance revealed a significant interaction between the diagnostic categories (unipolar, bipolar, and control) and sex in accounting for variation of the FCCP-evoked efflux. The diagnostic category X sex effect was also significant. The results reported indicate that the FCCP-evoked efflux of 5HT is an easily measured biochemical parameter of possible diagnostic interest.

Adult↗
PubMed1983

Cyclic GMP efflux from liver slices.

Cyclic GMP efflux from liver slices was studied when the intracellular cyclic GMP levels were elevated by incubation with N-methyl-N'-nitro-N-nitrosoguanidine (0.1 mM) and 3-isobutyl-1-methylxanthine (0.25 mM). A probenecid-sensitive and a probenecid-insensitive efflux system for cyclic GMP was found. It is suggested that the former system operates a carrier, which is saturable, the capacity of which is increased by alkylation with N-ethylmaleimide. The rate of net efflux of cyclic GMP increases 20-fold in the temperature interval 18-37 degrees C. Probenecid (0.5 mM) gives 50% inhibition of this system. The probenecid-insensitive cyclic GMP efflux component probably corresponds to passive diffusion. It appears that efflux may be an important complement to cyclic 3':5'-nucleotide phosphodiesterase activity in reducing intracellular cyclic GMP levels.

1-Methyl-3-isobutylxanthine↗