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A Lajtha

Publications and source records attributed to A Lajtha.

At least 145 records · Page 8Linked to original sources
PubMed1988

Effects of estradiol and dexamethasone on choline acetyltransferase activity in various rat brain regions.

Estradiol, administered to ovariectomized rats, increased choline acetyltransferase (ChAT) activity in the caudate nucleus, cortex, hippocampus, and hypothalamus, suggesting possibly widespread central cholinergic involvement in estrus-related behavior. Dexamethasone also, except in hypothalamus, increased ChAT activity, notably (50%) in hippocampus. ChAT activity changes did not correlate with reported regional hormone receptor density. Estradiol's effect in the caudate suggests that hormone receptor and affected enzyme may not necessarily coexist intraneuronally.

Animals↗
PubMed1988

Interaction of yohimbine with batrachotoxinin binding to mouse brain sodium channels.

To study the local anesthetic properties of yohimbine in more detail, its effect was examined in vitro on the scorpion toxin-enhanced specific binding of [3H]batrachotoxinin A 20-alpha-benzoate [( 3H]BTX-B) to the gating complex in sodium channel preparations from mouse brain cortex. Both equilibrium and kinetic experiments were carried out. Yohimbine inhibited the specific binding of [3H]BTX-B in the vesicular preparation with an IC50 value of 2.2 X 10(-5) M. This is about one order of magnitude higher than the concentration required for antagonism via the alpha 2-adrenoceptors; however, yohimbine is 7-fold more potent in inhibiting [3H]BTX-B binding than lidocaine. In a concentration-dependent manner, yohimbine increased the dissociation constant (Kd) of high-affinity [3H]BTX-B binding without changing the maximal binding capacity (Bmax). The dissociation rate constant was not affected by yohimbine, suggesting competitive inhibition as opposed to the action of local anesthetics involving an allosteric action via receptor sites distinct from the BTX site. Alpha 2-adrenoceptors are apparently not involved because clonidine and alpha-methyl-noradrenaline had no appreciable effect on [3H]BTX-B binding and did not antagonize the inhibitory effect of yohimbine. The present findings indicate a mechanism of local anesthetic action of yohimbine that differs from that of other local anesthetics such as tetracaine and lidocaine involving direct binding to the BTX site, thereby stabilizing a non-permeable form of the sodium channel.

Adrenergic alpha-Agonists↗
PubMed1988

The mode of action of ethanol on batrachotoxinin-A benzoate binding to sodium channels in mouse brain cortex.

Since ethanol has local anesthetic activity its effect was examined in vitro on the scorpion toxin-enhanced specific binding of [3H]batrachotoxinin A 20-alpha-benzoate ([3H]BTX-B) to the gating complex in sodium channel preparations from mouse brain cortex by equilibrium and kinetic experiments. Ethanol inhibited the specific binding of [3H]BTX-B in a vesicular preparation with an IC50 value of 310 mM and a Hill number of 1.0. Ethanol increased the equilibrium dissociation constant of batrachotoxin in a concentration dependent manner without changing the maximal binding capacity and decreased the half-time of the aconitine-induced dissociation of [3H]BTX-B. Thus, ethanol acts as an apparent competitive inhibitor, allosterically affecting the [3H]BTX-B binding, like other local anesthetics. Results of competition experiments in the presence of different concentrations of ethanol and fixed concentration of tetracaine (and vice versa) are consonant with an interaction of ethanol and tetracaine with the same binding sites. Experiment carried out at 32, 37 and 42 degrees C indicated that the effect of ethanol is not mimicked by increasing the temperature.

Animals↗
PubMed1988

Major rat brain membrane-associated and cytosolic enkephalin-degrading aminopeptidases: comparison studies.

The major cytosolic and membrane-associated enkephalin-degrading aminopeptidases were purified in parallel by column chromatography successively on DEAE-cellulose, AH-Sepharose, hydroxylapatite, Sephadex G-200, Affigel Blue, AH-Sepharose, and hydroxylapatite. With the final hydroxylapatite column, the cytosol (S) and the membrane (M) enzymes could each be resolved into two peaks, one eluted with 0.05 M phosphate (SI, MI) and the other with 0.25 M phosphate (SII, MII). The overall purification, with Arg BNA as substrate, for the SI and MI was about 450-fold; for SII and MII, 1,200-fold. The yield for each enzyme was about 2%. the major protein integral units of the four enzymes are similar; they are single polypeptide chains with a molecular weight of 100,000 daltons. Their pH optimum, substrate specificity, and sensitivity to puromycin show that they are similar to lysosomal aminopeptidase (EC 3.4.11.-). The two forms of the cytosol and the membrane enzymes have slightly different kinetic constants. With the inhibitors, SII is more sensitive to proctolin, whereas MII is more sensitive to bestatin and Arg-Phe-Ala. Mn2+ activates SI on Met-enkephalin degradation, but inhibits SII, MI, and MII.

Aminopeptidases↗
PubMed1988

Acute reduction of brain substance P induced by nicotine.

Ten minutes after a single injection of 0.8 mg/kg nicotine SC (free base) the level of substance P-like immunoreactivity (SPLI) was reduced by 61-73% in rat caudate-putamen, nucleus accumbens, and olfactory tubercle, with smaller and not significant reductions in the frontal cortex, substantia nigra, and ventral tegmental area. The nicotinic receptor antagonist mecamylamine (1.0 mg/kg IP) prevented the reductions in SPLI. The rapidity and the degree of the changes in SPLI after nicotine exceed those previously reported for other agents and implicate substance P neurotransmission as a major component of nicotinic action.

Animals↗
PubMed1988

Protein synthesis rates in rat brain regions and subcellular fractions during aging.

In vivo protein synthesis rates in various brain regions (cerebral cortex, cerebellum, hippocampus, hypothalamus, and striatum) of 4-, 12-, and 24-month-old rats were examined after injection of a flooding dose of labeled valine. The incorporation of labeled valine into proteins of mitochondrial, microsomal, and cytosolic fractions from cerebral cortex and cerebellum was also measured. At all ages examined, the incorporation rate was 0.5% per hour in cerebral cortex, cerebellum, hippocampus, and hypothalamus and 0.4% per hour in striatum. Of the subcellular fractions examined, the microsomal proteins were synthesized at the highest rate, followed by cytosolic and mitochondrial proteins. The results obtained indicate that the average synthesis rate of proteins in the various brain regions and subcellular fractions examined is fairly constant and is not significantly altered in the 4 to 24-month period of life of rats.

Aging↗
PubMed1988

Perinatal anti-androgen treatment and genotype affect the mesotelencephalic dopamine system and behavior in mice.

Sex and strain differences in tyrosine hydroxylase activity (TH) of brain dopamine systems have been reported for mice. To investigate if there might be a causal relationship between perinatal androgen secretion and regional mesotelencephalic TH activity, BALB/cJ and C57BL/6ByJ male mice were treated perinatally with cyproterone, a steroidal anti-androgen (or vehicle), and orchiectomized at 1 month of age. Two-way analysis of variance indicated significant treatment and strain effects in the mesencephalon and tuber olfactorium: perinatal cyproterone treatment lowered TH activity, and BALB/cJ had higher regional TH activities than those of C57BL/6ByJ. The most prominent behavioral effects of cyproterone treatment were found in the expression of scratching, which was considerably increased in both strains. Possible implications of these results are discussed.

Animals↗
PubMed1988

Ascorbic acid and striatal transport of [3H] 1-methyl-4-phenylpyridine (MPP+) and [3H] dopamine.

The inhibition of uptake of [3H] dopamine and [3H] 1-methyl-4-phenylpyridine (MPP+) was examined in mouse striatal synaptosomal preparations. Kinetic analysis indicated that ascorbic acid is a noncompetitive inhibitor of [3H] MPP+ uptake. No inhibition of [3H] dopamine uptake is observed. The dopamine uptake blockers, GBR-12909, cocaine, and mazindol strongly inhibit (IC50 less than 1 uM) both [3H] dopamine and [3H] MPP+ transport. Nicotine, its metabolites, and other tobacco alkaloids are weak inhibitors (IC50 greater than 1 mM) except 4-phenylpyridine and lobeline, which are moderate inhibitors (IC50 = 3 to 40 uM) of both [3H] dopamine and [3H] MPP+ uptake. These similarities in potencies are in agreement with the suggestion that [3H] MPP+ and [3H] dopamine are transported by the same carrier. The differences observed in the alteration of dopaminergic transport and mazindol binding by ascorbic acid suggest that ascorbic acid's effects on [3H] MPP+ transport are related to translocation and/or dissociation processes occurring subsequent to the initial binding event.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1988

Evidence that there is no direct correlation between alpha 2-adrenoceptor antagonism and inhibition of voltage-dependent sodium channels.

Electrophysiological and biochemical evidence suggests that the voltage-dependent sodium channel is the site of local anesthetic action, and that there is pharmacological similarity between alpha-adrenoceptors and Na+-channels. Yohimbine, a non-selective alpha 2-adrenoceptor antagonist, with a structure similar to that of cocaine affects the sodium channel by a mechanism different from that of other local anesthetics including cocaine. Some structural analogues of yohimbine -berbane compounds- were found to be potent and selective alpha 2-adrenoceptor antagonists. In this work the local anesthetic properties of two berbane compounds (6c and 6d (CH-38083) from the paper of Vizi, Toth, Somogyi, Szabo, Harsing and Szantay, 1987) were examined and compared to those of yohimbine in vitro on scorpion venom-enhanced specific binding of [3H]batrachotoxinin A 20-alpha-benzoate [( 3H]BTX-B) to the voltage-sensitive sodium channel and on the veratridine-induced depolarization measured by the uptake of [3H]trimethylphenylphosphonium ion [( 3H]TPMP+) in mouse brain cortex. Both of the compounds inhibited the [3H]BTX-B binding with an IC50 of (approximately) 150 microM, which is more than four orders of magnitude higher than the concentration required for antagonism of a presynaptic alpha 2-adrenoceptor (7 nM). They are 15 times less potent in inhibiting [3H]BTX-B binding and 2.5 times less potent in inhibiting veratridine-induced depolarization than yohimbine.

Adrenergic alpha-Antagonists↗
PubMed1988

3-Mercaptopropionic acid administration into the caudate-putamen of the rat provokes dyskinesia.

The unilateral administration of 3-mercaptopropionic acid (MPA) through an implanted guide cannula into the caudate-putamen produced dyskinesia in the rat. Striatal GABA and dopamine were decreased and the dopamine metabolites 3,4-dihydroxyphenylacetic and homovanillic acid were increased on the MPA-injected side at 2-10 min after the onset of dyskinesia. The dyskinetic movements were blocked by GABA or alpha-aminooxaloacetic acid but not by glycine or haloperidol.

3-Mercaptopropionic Acid↗
PubMed1988

Selective protection of benzomorphan binding sites against inactivation by N-ethylmaleimide. Evidence for kappa-opioid receptors in frog brain.

Selective binding of [3H]bremazocine and [3H]-ethylketocyclazocine to kappa-opioid receptor sites in frog (Rana esculenta) brain membranes is irreversibly inactivated by the sulfhydryl group alkylating agent N-ethylmaleimide (NEM). Pretreatment of the membranes with kappa-selective compounds [ethylketocyclazocine (EKC), dynorphin (1-13), or U-50,488H] but not with [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO; mu specific ligand) or [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DADLE; delta specific ligand) strongly protects the binding of the radioligands against NEM inactivation. These results provide more evidence for the existence of kappa-opioid receptors in frog brain. The relatively high concentrations of NEM that are needed to decrease the specific binding of [3H]bremazocine together with the observation of an almost complete protection of its binding sites by NaCl suggest that bremazocine may act as an opioid antagonist in frog brain.

Animals↗
PubMed1988

Two groups of amino acids interact with GABA-A receptors coupled to t-[35S]butylbicyclophosphorothionate binding sites: possible involvement with seizures associated with hereditary amino acidemias.

Seven L-amino acids (Trp, Arg, Lys, Met, Ile, Val, and Phe) partially (28-81%) reversed the inhibitory action of 1 microM gamma-aminobutyric acid (GABA) on t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to rat brain membranes, with EC50 values ranging from 5 to 120 mM. D-Trp, D-Arg, D-Lys, D-Met, D-Val, and D-Phe were approximately equipotent with their L-isomers. Tyramine, phenethylamine, and tryptamine, the decarboxylation products of the aromatic amino acids (Tyr, Phe, and Trp, respectively), reversed the inhibitory action of 1 microM GABA on [35S]TBPS binding more potently than the parent amino acids (EC50 values = 1.5-3.0 mM). Human hereditary amino acidemias involving Arg, Lys, Ile, Val, and Phe are associated with seizures, and these amino acids and/or their metabolites may block GABA-A receptors. Five other L-amino acids (ornithine, His, Glu, Pro, and Ala) as well as Gly and beta-Ala inhibited [35S]TBPS binding with IC50 values ranging from 0.1 to 37 mM, and these inhibitions were reversed by the GABA-A receptor blocker R 5135 in all cases. The inhibitory effects of L-ornithine, L-Ala, L-Glu, and L-Pro were stereospecific, because the corresponding D-isomers were considerably less inhibitory. L-His, D-His, and L-Glu gave incomplete (plateau) inhibitions. Human hereditary amino acidemias involving L-ornithine, His, Pro, Gly, and beta-Ala are also associated with seizures, and we speculate that these GABA-mimetic amino acids may desensitize GABA-A receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1988

Aminothiols: synthesis and effect on chicken brain aminopeptidases.

An amino acid derivative, leucinethiol, was reported to be a strong inhibitor of aminopeptidase activity. In order to obtain selective inhibitors of various brain aminopeptidases, we tested the inhibition by amino acid analogs of brain aminopeptidase activity. In particular, we synthesized the trifluoroacetyl derivatives of phenylalaninol, tyrosinol, and leucinol; leucinethiol; and phenylalaninethiol and measured their effect on soluble puromycin-sensitive aminopeptidase S1 and SII purified in our laboratory. Two of the compounds, L-bis (1-thio-2-amino-4-methylpentane) dihydrochloride (TAMP) and L-bis (1-thio-2-amino-3-phenylpropane) dihydrochloride (TAPP), caused significant inhibition.

Amphetamines↗
PubMed1987

Binding sites for [3H]tetracaine in synaptosomal sodium channel preparations from mouse brain.

The present study was an attempt to answer the question whether the local anesthetic [3H]tetracaine labels sodium channels in mouse brain synaptosomes. Binding of [3H]tetracaine had a Kd of 0.19 microM and a Bmax ranging from 3.7 to 5.2 pmol/mg of protein. Local anesthetics other than tetracaine and cocaine-related compounds inhibited [3H]tetracaine binding with Hill numbers between 0.3 and 0.6. Initiation of the dissociation of [3H]tetracaine binding by an excess of unlabeled tetracaine resulted in non-linear curves. These results are consonant with site heterogeneity, negative cooperativity, or complexities arising from the use of synaptosomal preparations instead of broken membranes. There were important differences between the absolute values of the potency of various local anesthetic drugs and cocaine-related compounds in inhibiting binding of [3H]tetracaine and those in inhibiting binding of [3H]batrachotoxinin A 20-alpha-benzoate. Although there were some effects of manipulating the state of the channel with activating toxins on the apparent rate of association and dissociation of [3H]tetracaine binding, the equilibrium binding was not much affected by the toxins. The results indicate that further characterization is necessary before accepting [3H]tetracaine binding as a valid tool for studying sodium channels.

Anesthetics, Local↗
PubMed1987

Autoradiographic distribution of binding sites of [3H]SKF 38393, a selective dopamine D1 receptor agonist, in the mouse forebrain.

Distribution of binding sites of [3H]SKF 38393, a selective dopamine D1 receptor agonist, was studied on forebrain coronal sections of CXBI/ByJ mice by radioligand binding and digital subtraction autoradiography. Highest levels of [3H]SKF 38393 binding were detected in olfactory tubercle and caudate nucleus/putamen. Intermediate to low concentrations of receptors were indicated in cortex, amygdala, hypothalamus, claustrum, and septal area, whereas the lowest binding was found in white matter tracts (commissura anterior, corpus callosum). Analysis of data on caudate nucleus/putamen indicates a striosomal pattern of binding with a gradient of binding sites from medial to lateral caudate/putamen. The distribution of [3H]SKF 38393 binding sites corresponds to that of dopaminergic projection fields in the studied areas.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1987

Depolarization of brain cortex slices and synaptosomes by lithium. Determination of K+-equilibrium potential in cortex slices.

K+-equilibrium potential was determined in brain cortex slices of rat by measuring 86Rb+ distribution between the extra- and intracellular space. The ratio of internal to external Rb+ concentration was 39 +/- 1.8, corresponding to a resting membrane potential of 93.8 mV. Li+ (1-126 mM) decreased the membrane potential in both cortex slices and synaptosomes in a concentration-dependent manner. The presence of 1 mM Li+ was enough to cause a slight but distinct depolarization. During incubation in Li+-containing medium slices took up K+; however, for depolarization the presence of extracellular Li+ seemed to be necessary.

Animals↗