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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a growing evidence that central nervous system chloride transport via gamma-aminobutyric acid (GABAA) related Cl- conductance or Cl-/HCO3- exchange affects anesthetic requirements. To delineate the effects of GABAA-related Cl- conductance blockade versus Cl-/HCO3- exchange inhibition, we determined the change in minimum alveolar anesthetic concentration (MAC) of halothane in rats after intracisternal infusion of 4,4'-diisothiocyano-2,2'-disulfonic acid stilbene (DIDS). DIDS inhibits Cl-/HCO3- exchange transport in concentrations greater than 1 microM and in GABAA-related Cl- channels in concentrations greater than 0.1 mM. After control MAC determination, rats were given intracisternal mock cerebrospinal fluid (n = 6), 1.0 microM DIDS (n = 8), or 1 mM DIDS (n = 8) at a rate of 2 microL/min for 30 min. Mock cerebrospinal fluid did not change the MAC of halothane. The MAC of halothane increased significantly (P less than 0.001) from 0.96% +/- 0.02% to 1.11% +/- 0.03% (mean value +/- SEM) with 1 microM DIDS and from 0.94% +/- 0.02% to 1.16% +/- 0.04% with 1 mM DIDS. The increases in MAC with 1 microM and 1 mM DIDS were not statistically different. This suggests that Cl-/HCO3- exchange inhibition increases halothane requirements, whereas GABAA-related Cl- channel blockade does not.
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PMID:Effect of chloride transport blockade on the MAC of halothane in the rat. 161 35

Previous studies have demonstrated that bupivacaine administered directly into the central nervous system (CNS) is capable of producing signs of bupivacaine cardiovascular toxicity. To investigate the mechanisms by which bupivacaine may act within the CNS to produce cardiovascular toxicity, we studied four groups of halothane-anesthetized rabbits in which infusion of intracerebroventricular (icv) bupivacaine or intravenous (iv) phenylephrine resulted in dysrhythmias and hypertension. In group 1 (n = 5), icv bupivacaine (500 +/- 79 micrograms [mean +/- SEM]) produced dysrhythmias lasting 73 +/- 13 min, whereas icv saline caused no dysrhythmias or hypertension. In group 2 (n = 9), icv bupivacaine-induced hypertension and dysrhythmias were abolished by icv midazolam in 4.4 +/- 0.6 min, and when dysrhythmias and hypertension recurred (22 +/- 0.9 min), hexamethonium (10 mg/kg iv) promptly terminated dysrhythmias and hypertension (14 +/- 1 s). In group 3 (n = 10), icv bupivacaine-induced dysrhythmias and hypertension were not affected by increasing the inspired halothane concentration from 0.8 to 1.6%. In group 4 (n = 6), iv phenylephrine-induced dysrhythmias and hypertension were not affected by icv midazolam. These results suggest that icv bupivacaine produces dysrhythmias and hypertension by increasing autonomic nervous system (ANS) outflow from the brain stem. The finding that peripheral autonomic blockade by hexamethonium rapidly terminated dysrhythmias and hypertension supports this mechanism. We speculate that icv bupivacaine produces an increase in autonomic outflow by blockade of the inhibitory gamma-aminobutyric acid (GABA) neurons that are known to be the principal tonic inhibitors of the ANS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hexamethonium and midazolam terminate dysrhythmias and hypertension caused by intracerebroventricular bupivacaine in rabbits. 167 Sep 15

The release of putative neurotransmitters [aspartate, glutamate, and gamma-aminobutyric acid (GABA)] was studied in hippocampal slices from adult normal C57BL/6J (B6) and El (epileptic) mice. The El mice, a genetic model of temporal lobe epilepsy, had an average of 86 seizures. Sets of B6 and El hippocampal slices (400 microns thick) were incubated in a series of normal and high potassium (60 mM) buffers in the presence or absence of calcium. The calcium-dependent and calcium-independent potassium-induced release of amino acids was compared in each mouse strain. Release of endogenous amino acids was measured using liquid chromatography with electrochemical detection and was expressed as picomoles of amino acid released per milliliter of incubation buffer per minute of incubation per slice +/- SEM. No significant differences were found between the El and B6 mice for the calcium-dependent potassium-evoked release of glutamate (18.20 +/- 2.62 and 15.41 +/- 3.56), or GABA (17.28 +/- 2.90 and 12.73 +/- 1.37), respectively. Aspartate release, however, was significantly higher in the El mice (6.62 +/- 0.69) than in the B6 mice (3.31 +/- 0.72). These findings suggest that enhanced aspartate release may be related to seizure expression in El mice.
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PMID:Enhanced aspartate release from hippocampal slices of epileptic (El) mice. 167 82

A massive striatal dopamine release (241-fold increase) was observed in a previous study during acute cerebral ischemia in rats. In this study, extracellular levels of glutamic acid (GLU), gamma-aminobutyric acid (GABA) and lactic acid were simultaneously determined using in vivo brain dialysis in the striatum of spontaneously hypertensive rats during cerebral ischemia and after recirculation. Extracellular GABA levels increased to 932 +/- 75% (mean +/- SEM) of the resting level and GLU increased to 390 +/- 63% during 20 min ischemia. Although ischemia-induced release of GLU and GABA was demonstrated in this study, the degree of increase was smaller than that of dopamine. These findings may be relevant to the pathophysiology of cerebral ischemia in the striatum.
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PMID:Striatal glutamic acid and gamma-aminobutyric acid in transient cerebral ischemia in spontaneously hypertensive rats. 197 32

Current and voltage-clamp recordings were made at room temperature from cultured mouse spinal neurons using conventional two-electrode voltage-clamp techniques and electrodes filled with either 3 M KCl, 3 M CsCl, or 3 M Cs2SO4. In the presence of tetraethylammonium and tetrodotoxin, "fast" (rapidly rising and falling) action potentials (FAP) of variable duration were recorded in most neurons. "Slow" (slowly rising and falling) depolarizing potentials (SDP) occurred in 23% of the cells, when using KCl-filled electrodes, and in 82% of the cells with CsCl-filled electrodes. The SDP was frequently preceded by an FAP, although in some cells activation of the SDP occurred before the FAP threshold was reached and in a graded fashion. Both the FAP and SDP were abolished by Cd2+ and other Ca2+ antagonists. In cells exhibiting SDPs, voltage-clamp analysis revealed a sustained (noninactivating) inward current (Isin) during depolarizing steps to potentials more positive than -45 mV. Repolarizing steps resulted in slowly decaying inward tail currents (Itail). Both Isin and Itail were abolished in solutions nominally free of Cao2+, or containing Ca2+-channel antagonists. Bao2+ did not support Isin. The data indicated a U-shaped activation curve for Isin, peaking at about -10 mV. Activation of Isin occurred exponentially with a time constant of approximately 140 ms at -23 mV, becoming faster at more depolarized potentials (ca. 50 ms at -2 mV). Deactivation was slow, giving rise to tail currents lasting seconds. In some cases deactivation could be described by a single exponential process, although frequently the kinetics were more complex. Deactivation was faster at hyperpolarized potentials and sensitive to extracellular ([Ca2+]o), duration of activating voltage steps, and the degree of activation of Isin. Using CsCl-filled electrodes, the reversal potential (Erev) for Isin was -1.7 mV (SEM 3.5 mV, n = 20). Erev always corresponded to the reversal potential for gamma-aminobutyric acid-evoked currents in the same cell. In experiments in which Cs2SO4-filled electrodes were used, Erev was estimated to be -44 mV (SEM 2.3 mV, n = 9). Neither complete substitution of Nao+ with choline ions nor elevation of [K+]o 10-fold significantly affected the estimated Erev. However, substitution of Cl0- with isethionate or methanesulphonate increased the amplitude of inward currents (recorded with CsCl-filled electrodes) and shifted Erev to more depolarized potentials. The results indicate that Cl- are the primary charge carriers for this current and that Cai2+ is required for its activation, leading us to identify it as ICl(Ca).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Voltage-clamp analysis of a Ca2+- and voltage-dependent chloride conductance in cultured mouse spinal neurons. 242 20

Brain gamma-aminobutyric acid (GABA) receptor density, affinity, and function, and plasma GABA-like activity were determined in rats with acute hepatic encephalopathy induced by an intraperitoneal injection of thioacetamide. In addition, the effect of various stress factors on brain GABA binding was assessed. Plasma GABA-like activity was significantly increased in rats with thioacetamide-induced hepatic encephalopathy compared with rats injected with vehicle alone (1506 +/- 993 nM, n = 7 vs. 367 +/- 97 nM, n = 9, mean +/- SD; p less than 0.001). In contrast, there were no alterations in either brain GABA receptor binding or in GABA-enhanced benzodiazepine binding in rats with hepatic encephalopathy when compared with relevant controls. However, rats that had received intraperitoneal injections of thioacetamide or vehicle (0.15 M NaCl) had significantly more low-affinity GABA receptors than rats that had neither been injected nor handled before killing (8769 +/- 1101 vs. 2710 +/- 757 fmol/mg protein, mean +/- SEM, p less than 0.001). We concluded that stress factors appear to be important causes of altered brain GABA binding. Brain GABA receptor binding and function, however, are unaltered in rats with thioacetamide-induced hepatic encephalopathy despite elevated plasma GABA-like activity.
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PMID:Brain gamma-aminobutyric acid receptor binding is normal in rats with thioacetamide-induced hepatic encephalopathy despite elevated plasma gamma-aminobutyric acid-like activity. 282 Aug 27

Specific somatostatin (SRIH) receptors on human pituitary adenoma cell membranes were characterized using [125I]Tyr11-SRIH as the radioligand. Specific binding of [125I] Tyr11-SRIH to adenoma cell membranes reached a steady state within 30 min at 25 C, and semilogarithmic analysis of the data revealed that the rate of the binding was linear at 25 C with a t1/2 of 13.2 min. Specific binding increased linearly with 5-160 micrograms plasma membrane protein. SRIH-14 and SRIH-28 inhibited [125I]Tyr11-SRIH binding to adenoma cell membranes with ID50S of 0.32 and 0.50 nM, respectively, while secretin, glucagon, gastrin, cholecystokinin-8, bombesin, TRH, LHRH, human GH-releasing factor-(1-44)-NH2, D-Ala2-met-enkephalin, gamma-aminobutyric acid and taurine did not significantly inhibit binding. All of 13 GH-secreting adenomas investigated had specific and high affinity SRIH receptors, with a dissociation constant (Kd) of 0.80 +/- 0.15 nM (mean +/- SEM) and a maximal binding capacity (Bmax) of 234.2 +/- 86.9 fmol/mg protein (mean +/- SEM). Among five of the nonsecreting pituitary adenomas examined, two had SRIH receptors with Kd values of 0.18 and 0.32 nM and Bmax values of 17.2 and 48.0 fmol/mg protein, respectively. In the remaining three, SRIH receptors were not detected. These results indicate that GH-secreting adenomas as well as some nonfunctioning adenomas have specific SRIH receptors, and hence, the function of the adenomas could be altered by SRIH.
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PMID:Specific somatostatin receptors on human pituitary adenoma cell membranes. 286 81

Imidazoleacetic acid (IAA) was unequivocally demonstrated in rat brain, human CSF, and human plasma by a gas chromatographic-mass spectrometric method that can reliably quantify as little as 8 pmol, i.e., 1 ng. Owing to tautomerism of the imidazole ring, IAA and [15N, 15N]IAA, the internal standard, each formed two chromatographically distinct isomers after derivatization of the ring nitrogens with either ethyl chloroformate or methyl chloroformate. The isomers of n-butyl(N-ethoxycarbonyl)imidazole acetate and n-butyl(N-methoxycarbonyl)imidazole acetate were identified by analysis with methane chemical ionization and electron impact ionization of molecular and fragment ions. The levels (mean +/- SEM) of free IAA were 140 +/- 14 pmol/g and 2.7 +/- 0.2 pmol/ml in brains of untreated rats and human lumbar CSF, respectively. Mean levels of IAA in brains of anesthetized rats, perfused free of blood, did not differ significantly from mean levels of anesthetized, nonperfused controls or from untreated rats. The source or sources of IAA in brain and CSF are unknown. Because IAA is a potent agonist at gamma-aminobutyrate receptors, it merits examination as a regulator in brain.
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PMID:Presence and measurement of imidazoleacetic acid, a gamma-aminobutyric acid agonist, in rat brain and human cerebrospinal fluid. 292 92

Male Fischer-344 rats aged 6, 12, or 24 months were subjected to four-vessel occlusion cerebral ischemia to assess age-dependent ischemic vulnerability of cholinergic and GABAergic neurons based on choline acetyltransferase (EC 2.3.1.6) and glutamic acid decarboxylase (EC 4.1.1.15) activities. Activities of both enzymes were similar (p greater than 0.05) in 6- (n = 5) and 12- (n = 5) month-old rats. Mean +/- SEM choline acetyltransferase activities in the cortex, hippocampus, striatum, and cerebellum of 6-month-old controls were 75 +/- 5, 123 +/- 9, 415 +/- 9, and 50 +/- 4 nmol acetylcholine/hr/mg protein, respectively, and were 20-30% lower (p less than 0.05) in all brain regions except the cerebellum in 24-month-old controls. Choline acetyltransferase activity was unaffected by ischemia in 6- and 12-month-old rats but was reduced by 30-60% in 24-month-old rats. Mean +/- SEM glutamic acid decarboxylase activities in the cortex, hippocampus, striatum, and cerebellum of 6-month-old controls were 98 +/- 8, 86 +/- 7, 144 +/- 13, and 125 +/- 9 nmol gamma-aminobutyric acid/hr/mg protein, respectively, and 25-35% lower in all regions of 24-month-old controls. After 30 minutes of ischemia and 5 days of recovery, glutamic acid decarboxylase activities were reduced (p less than 0.05) in all brain regions and age groups. However, its activity was decreased (p less than 0.05 compared with age-matched controls) by 55% in the cortex and 79% in the hippocampus of 24-month-old rats compared with 30% and 45% in younger rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Age-dependent vulnerability of brain choline acetyltransferase activity to transient cerebral ischemia in rats. 292 26

Cortical neurons using the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) are known to contribute to the formation of neuronal receptive field properties in the primary visual cortex (area 17) of the cat. In order to determine the cortical location of GABA containing neurons and what proportion of cortical neurons might use GABA as their transmitter, we analysed their distribution quantitatively using a post-embedding GABA immunohistochemical method on semithin sections in conjunction with stereological procedures. The mean total numerical density of neurons in the medial bank of the lateral gyrus (area 17) of five adult cats was 54,210 +/- 634 per mm3 (mean +/- SD). An average of 20.60 +/- 0.48% (mean +/- SEM) of the neurons were immunoreactive for GABA. The density of GABA-immunoreactive neurons was somewhat higher in layers II, III and upper VI, compared with layers I, IV, V and lower VI, with the lowest density being in layer V. The proportion of GABA-immunopositive cells relative to immunonegative neurons gradually decreased from the pia to the white matter. Layer I was different from other layers in that approximately 95% of its neurons were GABA-immunoreactive. The results allowed the calculation of the absolute numbers of GABAergic neurons in each layer under a given cortical surface area and could provide the basis for the quantitative treatment of cortical circuits.
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PMID:Quantitative distribution of GABA-immunoreactive neurons in the visual cortex (area 17) of the cat. 300 16


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