Search PubMed⌕ Search

Biomedical subjects

T Bartfai

Publications and source records attributed to T Bartfai.

At least 181 records · Page 10Linked to original sources
PubMed1988

Muscarinic receptors and receptor-mediated actions on rat thymocytes.

Rat thymocytes possess a single class of saturable, high affinity binding sites for muscarinic antagonists of the benzilate type such as [3H]3-quinuclidinyl benzilate ([3H]3-QNB). The average number of receptors per cell is 3000 and the equilibrium dissociation constant of [3H]3-QNB on intact cells is 7.5 nM. In the work reported here we found that perturbation of the thymocyte membrane by addition of phytohemagglutinin (4 micrograms/ml) caused a transient increase in muscarinic antagonist binding, and hydrocortisone (100 mg/kg s.c.) treatment of rats for 2 days prior to sacrifice increased the average number of muscarinic receptor sites on thymocytes by 100%. Atropine treatment, which in other tissues causes increased muscarinic receptor concentration, did not alter the receptor number on thymocytes. Binding of carbachol to the receptor on intact cells resulted in inhibition of cAMP synthesis and stimulation of cGMP synthesis. These muscarinic agonist effects were each inhibited by the simultaneous addition of the muscarinic antagonist atropine (5 X 10(-5) M). No stimulation of phosphatidylinositol turnover by muscarinic agonists was observed.

Animals↗
PubMed1988

Rat thymocytes release a factor which inhibits muscarinic ligand binding.

Rat thymocytes incubated in RPMI medium for 120-300 min release a soluble factor of molecular weight below 10,000 Da which inhibits the binding of 3H-labeled muscarinic antagonists in an uncompetitive manner, i.e. it reduces maximal specific binding (Bmax) without changing the affinity of the ligand (KD). This factor inhibited muscarinic antagonist binding on thymocytes and rat cerebral cortex cellular membranes. Thymocytes from hydrocortisone-treated rats produced more factor per mg cell protein than thymocytes from untreated rats. The activity of the factor was unaffected by incubation with Cd2+ (1 mM) or Zn2+ (1 mM) or EDTA (1 mM), and its protein nature is supported by the following findings: it was trypsin sensitive, heat denaturated at 56 degrees C and precipitated by (NH4)2SO4 (40%, w/v). Inhibition by the factor was apparently irreversible after 1 h of incubation.

Animals↗
PubMed1988

Use of synthetic peptides to map antigenic sites of Bordetella pertussis toxin subunit S1.

We synthesized six peptides (15-22 amino acids) from the amino acid sequence of the S1 subunit of pertussis toxin. The antigenicity of the polypeptides was investigated by enzyme-linked immunosorbent assays, in which the polypeptides coupled to bovine serum albumin were used as coating antigens. The polypeptides were examined as antigens for reaction with pre- and postvaccination sera from infants receiving either a Bordetella pertussis whole-cell vaccine or a vaccine containing pertussis toxoid. An elevated serum titer was noted upon vaccination with both types of vaccines when bovine serum albumin conjugates of five synthetic peptides were used as antigens. Similarly, mice immunized with whole-cell pertussis vaccine showed an elevated titer against all five peptides that were reactive with human sera. Thus, we identified five peptide sequences of S1 against which, in two species, antibodies are formed upon exposure of these species to whole cells of B. pertussis.

Animals↗
PubMed1988

Chronic exposure to pertussis toxin alters muscarinic receptor-mediated regulation of cyclic AMP metabolism in neuroblastoma x glioma NG108-15 hybrid cells.

Chronic pertussis toxin treatment (5 days) of NG108-15 neuroblastoma X glioma hybrid cells had no significant effect on basal cyclic AMP levels whereas it effectively blocked the inhibitory action of acute (10 min) exposure of carbachol (10(-4)M) on intracellular cyclic AMP accumulation, stimulated by prostaglandin E1. This action of pertussis toxin was found to be long lasting: exposure of the cells to pertussis toxin (100 ng/ml) for only 24 h followed by a 5-day withdrawal period still was shown effective on day 7 in abolishing the inhibitory action of carbachol on prostaglandin E1-stimulated cyclic AMP production. Chronic exposure (5 days) of NG108-15 cells to carbachol (10(-5)M) causes an increase in basal cyclic AMP levels by 98%, and a desensitization of the muscarinic inhibition of cyclic AMP accumulation, assessed after a 24-h withdrawal period. When carbachol treatment is carried out in the presence of pertussis toxin (100 ng/ml) both of these effects of carbachol are abolished.

1-Methyl-3-isobutylxanthine↗
PubMed1988

Substance P receptors in the rat spinal cord: the effect of GTP and of chronic antidepressant treatment.

Substance P receptors were examined in crude synaptosomal fraction preparations of the rat spinal cord using [125I]Bolton Hunter Substance P ([125I]BHSP) which binds with an affinity of 0.043 +/- 0.015 nM. The concentration of binding sites in the dorsal and in the ventral part was 4.55 +/- 0.86 and 2.35 +/- 0.35 fmol mg-1, respectively. GTP inhibited the specific binding of [125I]BHSP in a concentration dependent manner, with 10(-3) mol l-1 GTP yielding 89-90% inhibition and 10(-5) mol l-1 GTP producing 50% inhibition. This value was similar in dorsal and ventral spinal cord. The effects on SP receptors of chronic treatment with the tricyclic antidepressant imipramine (2 x 10 mumol kg-1 day-1 p.o. 14 days) and the specific 5-HT (serotonin) uptake blockers alaproclate (2 x 20 mumol kg-1 day-1 p.o. 14 days) and zimelidine (2 x 10 mumol kg-1 day-1 p.o. 14 days) were examined in the ventral spinal cord, where SP and 5-HT coexist in the terminals of descending neurons from the raphe nucleus. Zimelidine treatment was found to cause a significant reduction in the number of substance P binding sites in the rat ventral spinal cord as compared to saline treated controls. These findings are discussed in light of the previous observation (Brodin et al. 1984) that SP levels are significantly elevated after treatment with antidepressant drugs especially with zimelidine, which alters the firing rates of 5-HT and 5-HT/SP neurons.

Alanine↗
PubMed1988

Neuropeptide Y and peptide YY inhibit adenylate cyclase activity in the rat striatum.

The equilibrium binding of [3H]propionyl neuropeptide Y ([ 3H]pNPY) to receptors in a crude synaptic membrane preparation from the rat striatum was influenced by GTP, which caused an apparent loss of high-affinity binding sites for [3H]pNPY. In the presence of GTP (10(-5) M), NPY and peptide YY (PYY) inhibited basal and forskolin-stimulated adenylate cyclase activity in a concentration-dependent manner in a cell-free preparation from rat striatum. The IC50 values for NPY and PYY were 1 X 10(-8) M and 1.4 x 10(-8) M respectively. The inhibitory action of NPY (10(-6) M) or of PYY (10(-6) M) was additive to that of acetylcholine (10(-4) M). The two peptides together also showed additivity (P less than 0.05) in inhibiting adenylate cyclase.

Adenylyl Cyclases↗
PubMed1987

Increased affinity of choline acetyltransferase for choline in Alzheimer's disease: a steady-state kinetic study.

The steady-state kinetics of choline acetyltransferase (CAT) from autopsy samples of human caudate nucleus of aged controls and of patients with Alzheimer's disease was studied. In 10 samples from Alzheimer's disease-afflicted brains the affinity for the limiting substrate choline (Ch) was significantly higher: Michaelis constant KmCh was for these samples 1.93 +/- 0.72 mM while in the samples from 9 age-matched controls KmCh was 2.53 +/- 0.78 mM. The difference is statistically significant (P less than 0.05). Endogenous choline concentrations in the samples were 124 +/- 39 (n = 10) nmol/g wet wt. in the Alzheimer's disease-afflicted samples and 180 +/- 57 (n = 9) nmol/g wet weight (n = 9) in the control samples (P less than 0.05). The initial velocity at 70 microM acetyl co-enzyme (AcCoA) in Alzheimer's samples was 171.5 +/- 131.0 pmol [14C]acetyl choline [14C]ACh/mg protein/min as compared to the controls 422.1 +/- 231.0 pmol [14C]ACh/mg protein/min replicating many previous findings about decline of CAT activity in Alzheimer's disease. However, in the same samples the affinity for the other substrate acetyl-CoA (AcCoA) was significantly lower for the Alzheimer patients, KmAcCoA = 61 +/- 40 microM, than for the age-matched control patients, KmAcCoA = 28 +/- 8 microns (P less than 0.01). The data suggest some compensation of the loss of enzyme molecules via changed affinity for the limiting substrate, Ch.

Aged↗
PubMed1987

Coexistence of peptides with classical neurotransmitters.

In the present article the fact is emphasized that neuropeptides often are located in the same neurons as classical transmitters such as acetylcholine, 5-hydroxy-tryptamine, catecholamines, gamma-aminobutyric acid (GABA) etc. This raises the possibility that neurons produce, store and release more than one messenger molecule. The exact functional role of such coexisting peptides is often difficult to evaluate, especially in the central nervous system. In the periphery some studies indicate apparently meaningful interactions of different types with the classical transmitter, but other types of actions including trophic effects have been observed. More recently it has been shown that some neurons contain more than one classical transmitter, e.g. 5-HT plus GABA, further underlining the view that transfer of information across synapses may be more complex than perhaps hitherto assumed.

Animals↗
PubMed1987

Neuropeptide Y receptors and the inhibition of adenylate cyclase in the human frontal and temporal cortex.

The presence of a single class of high affinity, saturable binding sites for [3H]neuropeptide Y (NPY) was demonstrated in membranes from human frontal and temporal cortex. The specific binding of [3H]NPY was sensitive to guanosine 5'-triphosphate (GTP) and guanylyl-imidodiphosphate (GMPP(NH)P; 100 microM) which lowered the total binding capacity (Bmax) value (35 +/- 2 fmol/mg in the frontal cortex and 82 +/- 3 fmol/mg in the temporal cortex) by 50%. GTP and GMPP(NH)P did not affect the dissociation constant (Kd) value which was 0.25 +/- 0.03 nM in a frontal cortex sample and 0.76 +/- 0.06 nM in the sample from the temporal cortex. The affinity and GTP sensitivity of the [3H]NPY binding to human brain membranes parallels that found in the rat brain. It was demonstrated that occupancy of NPY receptors by NPY (1 microM) inhibits the basal and forskolin (10 microM)-stimulated adenylate cyclase activity by 18-30% in a crude membrane preparation from human frontal cortex.

Adenosine Triphosphate↗
PubMed1987

Tachykinin regulation of serotonin release: enhancement of [3H]serotonin release from rat cerebral cortex by neuromedin K and substance P acting at distinct receptor sites.

Neuromedin K and substance P (SP) enhanced the basal (5 mM K+) and potassium-evoked (40 mM K+) release of [3H]5-hydroxytryptamine ([3H]5-HT) from slices of the rat cerebral cortex. The effects of the two tachykinins were additive. The SP antagonist span-tide ([D-Arg1, D-Trp7.9, Leu11]-SP) (10(-6) M) inhibited the stimulatory effect of SP but not of neuromedin K on the release of [3H]5-HT. These findings suggest that the two tachykinins exhibit their effects on serotonin release at distinct receptor sites.

Animals↗
PubMed1987

Evidence for an inhibitory effect of the peptide galanin on dopamine release from the rat median eminence.

The role of the neuropeptide galanin (GAL) in rat hypothalamus has been studied in different experimental models. Thus, the effect of GAL on potassium-induced dopamine release was analyzed in vitro, and the localization of GAL and GAL binding sites was studied with immunohistochemistry and receptor autoradiography, respectively. In the median eminence GAL and presumably dopamine were found to coexist in nerve endings and this area contained a high density of 125I-GAL binding sites. In vitro experiments revealed that GAL inhibited the release of [3H]dopamine in a dose-dependent manner (IC50 = 7-10 nM), possibly via a presynaptic receptor.

Animals↗
PubMed1987

Interleukin-1-like immunoreactivity in peripheral tissues.

Rabbit antisera were raised against a synthetic peptide corresponding to the amino acid residues 169-194 in the murine interleukin-1 sequence. Immunoreactive varicose fibers were observed in the vas deferens, urinary bladder, gastrointestinal tract, and coeliac-superior mesenteric ganglion complex of the rat. Fibers were also encountered around blood vessels in several organs including the thymus, spleen, lymph nodes, liver, and kidney.

Amino Acid Sequence↗
PubMed1987

BM-5, a centrally active partial muscarinic agonist with low tremorogenic activity. In vivo and in vitro studies.

The acute and chronic effects of the centrally active oxotremorine analog, BM-5, [N-methyl-N-(1-methyl-4-pyrrolidino-2-butynyl)-acetamide] were examined in rats and mice. In vivo studies in mice and rats indicated that this compound is a partial muscarinic agonist with large regional differences in its efficacy: BM-5 produced low tremor in doses which evoke full salivary response. The maximal tremor response to BM-5 was much smaller than that produced by oxotremorine, while the maximal salivary response to BM-5 was greater than that evoked by oxotremorine. The tremor response to BM-5 was bell-shaped, the peak dose being around 2 mg/kg. In contrast, the salivary response increased with increasing doses of BM-5. The apparent muscarinic antagonist properties of higher doses of BM-5 were specific to the striatum in which BM-5 (0.05-10 mg/kg) caused significant decreases in the level of acetylcholine while these levels were unaltered in the cerebral cortex, hippocampus, and brainstem. Pretreatment of rats with BM-5 (5 mg/kg) also prevented the increase in striatal acetylcholine induced by oxotremorine (0.75 mg/kg). Chronic treatment of mice with BM-5 (0.2-2 mg/kg) for 14 days also showed that BM-5 at higher doses, behaved as an antagonist, since it caused supersensitivity to oxotremorine on the tremor response. In addition, the number of receptor sites, as measured by binding of 3H-3-quinuclidinyl benzilate (3H-3-QNB), was increased in the striatum while no similar increase was observed in other brain areas.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1987

Galanin inhibits acetylcholine release in the ventral hippocampus of the rat: histochemical, autoradiographic, in vivo, and in vitro studies.

A high density of galanin binding sites was found by using 125I-labeled galanin, iodinated by chloramine-T, followed by autoradiography in the ventral, but not in the dorsal, hippocampus of the rat. Lesions of the fimbria and of the septum caused disappearance of a major population of these binding sites, suggesting that a large proportion of them is localized on cholinergic nerve terminals of septal afferents. As a functional correlate to these putative galanin receptor sites, it was shown, both in vivo and in vitro, that galanin, in a concentration-dependent manner, inhibited the evoked release of acetylcholine in the ventral, but not in the dorsal, hippocampus. Intracerebroventricularly applied galanin (10 micrograms/15 microliters) fully inhibited the scopolamine (0.5 mg/kg, s.c.)-stimulated release of acetylcholine in the ventral, but not in the dorsal, hippocampus, as measured by microdialysis technique. In vitro, galanin inhibited the 25 mM K+-evoked release of [3H]acetylcholine from slices of the ventral hippocampus, with an IC50 value of approximately 50 nM. These results are discussed with respect to the colocalization of galanin- and choline acetyltransferase-like immunoreactivity in septal somata projecting to the hippocampus.

Acetylcholine↗
PubMed1986

Presynaptic effects of neuropeptide Y on [3H]noradrenaline and [3H]acetylcholine release.

The electrically evoked release of radioactivity from mouse vas deferens and rat hypothalamic slices preloaded with [3H]noradrenaline was measured. In addition the release of [3H]acetylcholine from longitudinal muscle strip of guinea-pig ileum was also measured. Neurochemical evidence has been obtained that neuropeptide Y (NPY), although it co-exists and is released with (-)-noradrenaline (NA), it behaves differently as far as its effect on presynaptic modulation of chemical neurotransmission is concerned. It exerts a frequency-dependent presynaptic inhibitory effect on noradrenaline release from mouse vas deferens but has no effect on the electrically evoked release of NA from rat hypothalamus. Unlike NA, NPY does not influence the release of [3H]acetylcholine from the longitudinal muscle strip of guinea-pig ileum and does not potentiate the presynaptic effect of NA. It seems very likely, that the inhibitory effect of NPY is mediated via receptors. Its action is concentration dependent. While exogenous noradrenaline inhibited the release of noradrenaline by 91%, the maximum inhibition reached with NPY was not higher than 60%, indicating that either the intrinsic activity of NPY is lower or much less axon terminals are equipped with NPY receptors. Peptide YY (PYY) also reduced the release of NA from mouse vas deferens.

Acetylcholine↗
PubMed1986

Iodinated derivatives of the vasoactive intestinal polypeptide (VIP) are agonists at the cat pancreas and the rat submandibular salivary gland.

Porcine VIP was iodinated by the chloramine-T method. The reaction products, which were separated by high pressure liquid chromatography, included residual native VIP, oxidized VIP and at least two iodinated VIP species. The iodo-VIP derivatives were recognized by antibodies raised against VIP and by VIP receptors. Furthermore, they appear to be approximately equipotent agonists to VIP in activating the adenylate cyclase in membranes from the rat submandibular salivary gland and in the stimulation of pancreatic secretion in vivo.

Adenylyl Cyclases↗