Journal of neurochemistry
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Journal of neurochemistry · Apr 1989
Distribution and pharmacological properties of the GABAA/benzodiazepine/chloride ionophore receptor complex in the brain of the fish Anguilla anguilla.
In the present study, we characterized the distribution and the pharmacological properties of the different components of the GABAA receptor complex in the brain of the eel (Anguilla anguilla). Benzodiazepine recognition sites labeled "in vitro" with [3H]flunitrazepam ([3H]FNT) were present in highest concentration in the optic lobe and in lowest concentration in the medulla oblongata and spinal cord. A similar distribution was observed in the density of gamma-[3H]aminobutyric acid ([3H]GABA) binding sites. ⋯ Moreover, the uptake of 36Cl- into eel brain membrane vesicles was only marginally stimulated by concentrations of GABA or muscimol that significantly enhanced the 36Cl- uptake into rat brain membrane vesicles. Finally, intravenous administration of the beta-carboline inverse agonist 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylic acid methyl ester (20 mg/kg) and of the chloride channel blocker pentylenetetrazole (80 mg/kg) produced convulsions in eels that were antagonized by diazepam at doses five to 20 times higher than those required to produce similar effects in rats. The results may indicate a different functional activity of the GABA-coupled chloride ionophore in the fish brain as compared with the mammalian brain.
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Journal of neurochemistry · Nov 1988
Comparative StudyModulation of the benzodiazepine/gamma-aminobutyric acid receptor chloride channel complex by inhalation anesthetics.
Inhalation anesthetics, such as diethyl ether, halothane, and enflurane, increase 36Cl- uptake into rat cerebral cortical synaptoneurosomes in a concentration-dependent, picrotoxin-sensitive fashion. At concentrations consistent with those that stimulate 36Cl- uptake, inhalation anesthetics also inhibit the binding of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) to well-washed cortical membranes. ⋯ Nonetheless, there are differences between nonvolatile agents (such as barbiturates and alcohols) and inhalation anesthetics, because the former compounds augment muscimol (a GABAmimetic) stimulated 36Cl- uptake, whereas the latter group (such as ether and enflurane) inhibit this effect. These findings demonstrate that therapeutically relevant concentrations of inhalation anesthetics perturb the benzodiazepine/gamma-aminobutyric acid receptor chloride channel complex, and suggest this oligomeric protein may be a common mediator of some aspects of anesthetic action.
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Journal of neurochemistry · May 1988
Comparative StudyBrain metabolism and intracellular pH during ischaemia: effects of systemic glucose and bicarbonate administration studied by 31P and 1H nuclear magnetic resonance spectroscopy in vivo in the lamb.
Brain metabolism and intracellular pH were studied during and after episodes of incomplete cerebral ischaemia in lambs under sodium pentobarbitone anaesthesia. 31P and 1H magnetic resonance spectroscopy was used to monitor brain pHi and brain concentrations of inorganic phosphate (Pi), phosphocreatine (PCr), beta-nucleoside triphosphate (beta NTP), and lactate. Simultaneous measurements were made of arterio-cerebral venous concentration differences (AVDs) for oxygen, glucose, and lactate. Cerebral ischaemia was induced by a combination of bilateral carotid clamping and hypotension, and the acute effects of systemic administration of glucose and sodium bicarbonate were examined. ⋯ Administration of sodium bicarbonate systemically in the postischaemic period was associated with a rise in arterial and brain tissue PCO2. A fall in brain pHi occurred which was attributable in part to coincidental brain lactate accumulation. The increase in brain lactate measured by 1H nuclear magnetic resonance in vivo during ischaemia was insufficient to account for the change in buffer base calculated to have occurred from previous estimates of brain buffering capacity.
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Journal of neurochemistry · May 1988
Comparative StudyDephosphorylation of microtubule proteins by brain protein phosphatases 1 and 2A, and its effect on microtubule assembly.
Protein phosphatase C was purified 140-fold from bovine brain with 8% yield using histone H1 phosphorylated by the catalytic subunit of cyclic AMP-dependent protein kinase (cyclic AMP-kinase). Brain protein phosphatase C was considered to consist of 10 and 90%, respectively, of the catalytic subunits of protein phosphatases 1 and 2A on the basis of the effects of ATP and inhibitor-2. Protein phosphatase C dephosphorylated microtubule-associated protein 2 (MAP2), tau factor, and tubulin phosphorylated by a multifunctional Ca2+/calmodulin-dependent protein kinase (calmodulin-kinase) and the catalytic subunit of cyclic AMP-kinase. ⋯ The holoenzyme of protein phosphatase 2A from porcine brain could also dephosphorylate MAP2, tau factor, and tubulin phosphorylated by the two kinases. The phosphorylation of MAP2 and tau factor by calmodulin-kinase separately induced the inhibition of microtubule assembly, and the dephosphorylation by protein phosphatase C removed its inhibitory effect. These data suggest that brain protein phosphatases 1 and 2A are involved in the switch-off mechanism of both Ca2+/calmodulin-dependent and cyclic AMP-dependent regulation of microtubule formation.
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Journal of neurochemistry · Sep 1987
Changes in composition of endoneurial and perineurial fatty acids during glycerol-induced Wallerian degeneration and regeneration in the sciatic nerve of the adult rat.
Intraneural injection of pure glycerol induces Wallerian degeneration with subsequent regeneration. In agreement with other reports, we observed an increase in endoneurial polyunsaturated fatty acids 8 days after the glycerol injection. ⋯ The rise in C18:2(n-6) in endoneurium correlated with infiltration of this tissue by perineurial cells. Interactions between perineurium and endoneurium during nerve regeneration are discussed.