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Biomedical subjects

A Seregi

Publications and source records attributed to A Seregi.

33 records · Page 2Linked to original sources
PubMed1984

Anticonvulsive effects of endogenous prostaglandins formed in brain of spontaneously convulsing gerbils.

Seizures were induced in a strain of epileptic gerbils by moderate environmental stress. Concentrations of five different cyclooxygenase products (PGD2, PGF2 alpha, PGE2, 6-keto-PGF1 alpha and thromboxane B2) were measured in brain by specific radioimmunoassays before and at different time intervals after the onset of clonic-tonic convulsions. All prostanoids markedly increased subsequent to the convulsions. Maximal concentrations were reached after about 15 min. The major compound detected was PGD2, followed by PGF2 alpha and lower concentrations of the other cyclooxygenase products. Indomethacin completely prevented the convulsion-induced formation of prostanoids. Fifteen min after a first seizure almost all animals proved to be protected against a second convulsion. Indomethacin pretreatment markedly reduced the number of convulsion-resistant animals. These findings are compatible with the hypothesis that endogenous prostaglandins exert anticonvulsive effects.

Animals↗
PubMed1983

Evidence for the localization of hydrogen peroxide-stimulated cyclooxygenase activity in rat brain mitochondria: a possible coupling with monoamine oxidase.

The distribution of basal and of H2O2-stimulated cyclooxygenase activity in the primary fractions of rat brain homogenates and in the subfractions of crude mitochondrial fraction was studied. For comparison, the localization of H2O2-generating monoamine oxidase (MAO) as well as that of the mitochondrial marker succinate dehydrogenase (SDH) was also examined. H2O2 was generated by MAO using 5 x 10(-4) M noradrenaline (NA) or 2 x 10(-4) M 2-phenylethylamine (PEA) as substrates, or by 25 micrograms glucose oxidase (GOD) per ml in the presence of 1 mM glucose. For nonstimulated (basal) cyclooxygenase, the relative specific activity (RSA) was high in microsomes (1.79) and in the free mitochondria-containing subfraction of the crude mitochondrial fraction (1.94). Parallel distribution of MAO and H2O2-stimulated cyclooxygenase was observed in all fractions studied in the presence of NA. The highest RSA was found in the purified mitochondria for both enzymes (1.85 for MAO and 1.97 for H2O2-stimulated cyclooxygenase). The enrichment of SDH (RSA = 2.21) indicated a high concentration of mitochondria in this fraction. The same distribution of H2O2-stimulated cyclooxygenase was obtained when, instead of the MAO-NA system, hydrogen peroxide was generated by GOD in the presence of glucose. H2O2 generated by deamination of NA or PEA by MAO, or during the enzymatic oxidation of glucose by GOD, caused a threefold increase in mitochondrial endoperoxide formation. Indomethacin (2 x 10(-4) M), catalase (50 micrograms/ml), and pargyline (2 x 10(-4) M) eliminated the MAO-dependent mitochondrial synthesis of PG endoperoxides. The GOD-dependent cyclooxygenase activity in this fraction was abolished by indomethacin or catalase, but not by pargyline. The results show the existence of a mitochondrial cyclooxygenase in brain tissue. The enzyme is sensitive to H2O2 and produces prostaglandin endoperoxides from an endogenous source of arachidonic acid. The identical localization of H2O2-producing MAO and H2O2-sensitive cyclooxygenase suggests a possible coupling between monoamine and arachidonic acid metabolism.

Animals↗
PubMed1982

Receptor independent stimulatory effect of noradrenaline on Na,K-ATPase in rat brain homogenate. Role of lipid peroxidation.

The effect of different adrenoceptor agonists on Na,K-ATPase activity and lipid peroxidation of rat brain homogenate was studied. Drugs which enhanced Na,K-ATPase activity--noradrenaline, adrenaline and oxymethazoline--were found to inhibit endogenous membrane lipid peroxidation. Other drugs--phenylephrine, xylazine and clonidine--which did not cause any change in the enzyme activity did not influence lipid peroxidation either. No increase of Na,K-ATPase activity by noradrenaline could be detected after preincubation of the homogenate for 5 min at 37 degrees. During this time endogenous lipid peroxidation of considerable extent could be observed. It is concluded that there is no correlation between the adrenoceptor agonist feature of noradrenaline and its stimulatory effect on Na,K-ATPase activity of rat brain homogenate. However, it seems likely that in rat brain homogenate the increase of Na,K-ATPase activity and inhibition of endogenous lipid peroxidation by noradrenaline are related.

Adrenergic Agonists↗
PubMed1982

On the mechanism of the involvement of monoamine oxidase in catecholamine-stimulated prostaglandin biosynthesis in particulate fraction of rat brain homogenates: role of hydrogen peroxide.

The mechanism of involvement of monoamine oxidase (MAO) in catecholamine-stimulated prostaglandin (PG) biosynthesis was studied in the particulate fraction of rat brain homogenates. High concentrations of either noradrenaline (NA) or dopamine (DA) stimulated effectively PGF2 alpha formation. The same amount of 2-phenylethylamine (PEA) acted similarly, provided that it was administered together with a catecholamine analogue or metabolite possessing the 3,4-dihydroxyphenyl nucleus--3,4-dihydroxyphenylalanine (DOPA), 3,4-dihydroxyphenylacetic acid (DOPAC), 3,4-dihydroxyphenylglycol (DOPEG), 3,4-dihydroxyphenylacetaldehyde (DOPAL), or alpha-methylnoradrenaline (alpha-met-NA)--or with SnCl2. In the absence of PEA, these compounds were ineffective with regard to stimulation of PGF2 alpha formation. Catalase, pargyline, or indomethacin abolished completely PGF2 alpha formation elicited either by catecholamines or by PEA plus a 3,4-dihydroxyphenyl compound or SnCl2. With regard to the stimulation of PGF2 alpha formation in the presence of alpha-met-NA, PEA could be replaced by H2O2 generated by the glucose oxidase(GOD)-glucose system. The effect of H2O2 was inhibited by indomethacin or catalase, but pargyline was ineffective. It is assumed that catecholamines play a dual role in the activation of PG biosynthesis in brain tissue. During the enzymatic decomposition of catecholamines MAO produces H2O2, which stimulates endoperoxide synthesis. Simultaneously, catecholamines as hydrogen donors promote the nonenzymatic transformation of endoperoxides into PGF2 alpha. The possible physiological importance of these findings is discussed.

Animals↗
PubMed1982

Na-K activated ATPase and the release of acetylcholine and noradrenaline.

1. It has been shown that different experimental conditions known to inhibit Na-K-activated ATPase, and enzyme present in the neuronal membranes, are able to promote transmitter release (ACh, NA, etc.) from different tissues, simply by making the membrane leaky. 2. Under physiological conditions, Ca entering the cell transiently inhibits membrane ATPase, resulting in a transient change in membrane permeability and a subsequent release of transmitter. 3. When membrane ATPase inhibitor was used one part of the release proved to be Ca-independent. This finding indicates that the voltage and Ca-dependent link of transmitter release can be by-passed by direct membrane ATPase inhibitors (ouabain). 4. Neurochemical and electrophysiological evidence was obtained on mouse diaphragm that most of the released ACh is cytoplasmic and Na-K ATPase inhibition is responsible for its release. 5. The stimulation of membrane ATPase (by switching off K and its readmission) results in an inhibition of both ACh and noradrenaline release evoked by axonal stimulation. 6. It is suggested that, in those cases where the varicose axon terminals do not make synaptic contact, the transmitter released from the cytoplasmic pool contributes to the transmission, since during diffusion (sometimes few thousand nm) transmitter of different origins becomes mixed up.

Acetylcholine↗
PubMed1981

Studies on prostaglandin F2 alpha formation caused by pentametylenetetrazol-induced convulsions in rat brain.

Prostaglandin F2 alpha formation caused by pentametylenetetrazol convulsions was studied as a function of the duration, the doses of the convulsant and the intensity of the seizures. It was shown by the statistical analysis of the results in the case of clonic convulsions that the amount of synthetized PGF2 alpha did not depend on the doses of convulsant, while close relation existed between the duration and the PGF2 alpha production. At the same time, during tonic convulsions lasting longer than 50 sec, no more increase in the PGF2 alpha content of the brain was observed. An experimental model is suggested to study in vivo the mechanisms regulating the brain's prostaglandin biosynthesis. Pretreatment of the animals with reserpine did not affect the rate of convulsion-induced PGF2 alpha-formation.

Animals↗
PubMedDate not supplied

In vivo comparative study of the seizure- and ischemia-induced synthesis of eicosanoids in the brain of gerbils.

After transient cerebral ischemia induced by bilateral ligation of carotid arteries, followed by 5 min reperfusion, concentrations of prostaglandin D2 and LTC4-like material increased with time in the gerbil brain. At least a 1 min occlusion time was necessary to elevate the eicosanoid concentrations significantly over the basal levels. Spontaneous tonic-clonic seizures of about 20 sec duration induced an increase in prostaglandin D2 and LTC4-like material comparable to the values found after a 2 min occlusion time. Following carotid artery occlusion, the eicosanoid levels were found to be elevated in midbrain, hypothalamus, striatum, hippocampus and cortex, i.e., those brain areas dependent upon the blood supply from the carotid arteries. In contrast, following spontaneous seizures, prostaglandin D2 concentrations were increased in the striatum, hippocampus and cortex only, and the LTC4-like material in the cortex. Hippocampus, striatum and cortex are brain areas which participate in the generation and propagation of seizures. It appears, therefore, unlikely that the seizure-induced eicosanoid synthesis is triggered off by a hypoxic event due to an impaired breathing caused by convulsions. The regional pattern of the eicosanoid synthesis following the seizures may rather depend on the intensity of the neuronal activity than on regional differences in the eicosanoid-synthesizing capacity.

Animals↗