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

The contributions of NAD-specific and NADP-specific isocitrate dehydrogenases to isocitrate oxidation in isolated intact rat liver mitochondria were examined using DL-threo-alpha-methylisocitrate (3-hydroxy-1,2,3-butanetricarboxylate) to specifically inhibit flux through NADP-specific isocitrate dehydrogenase. Under a range of conditions tested with respiring mitochondria, the rate of isocitrate oxidation was decreased by about 20--40% by inhibition of NADP-isocitrate dehydrogenase, and matrix NADP became more oxidized. (a) For mitochondria incubated with externally added DL-isocitrate and citrate, the rate of isocitrate oxidation obtained by extrapolation to infinite alpha-methylisocitrate concentration was approximately 70% of the uninhibited rate in both state 3 and state 4. (b) With pyruvate plus malate added as substrates of citric acid cycle oxidation and isocitrate generated intramitochondrially, a concentration of alpha-methylisocitrate (400 microM) sufficient for 99.99% inhibition of NADP-isocitrate dehydrogenase inhibited isocitrate oxidation in states 4 and 3 by 21 +/- 6% and 19 +/- 11% (mean +/- SEM), respectively. (c) With externally added isocitrate and citrate, the addition of NH4Cl increased isocitrate oxidation by 3--4-fold, decreased NADPH levels by 30--40% and 2-oxoglutarate accumulation by about 40%. The further addition of 600 microM alpha-methylisocitrate decreased the NH4Cl-stimulated isocitrate oxidation by about 40% and decreased NADPH to about 30% of the level prevailing in the absence of NH4Cl; nevertheless, the rate of isocitrate oxidation was still twice as large in the presence of NH4Cl and alpha-methylisocitrate as in their absence. Experiments were also performed with intact mitochondria incubated with respiratory inhibitors to determine additional factors which might affect the flux through the two isocitrate dehydrogenases. (a) In the coupled reduction of acetoacetate by isocitrate, where the rate of reoxidation of reduced pyridine nucleotides is limited by NAD-specific 3-hydroxybutyrate dehydrogenase, 85--100% of the rate of 3-hydroxybutyrate formation was retained in the presence of 400--900 microM alpha-methylisocitrate. (b) In a system where the rate of isocitrate oxidation is limited by the rate of NADPH reoxidation by glutathione reductase, the rate of glutathione reduction extrapolated to infinite alpha-methylisocitrate concentration was from 20--40% of the uninhibited rate. (c) In the coupled synthesis of glutamate from isocitrate and NH4Cl, where the reoxidation of NADPH and NADH can occur via glutamate dehydrogenase, the rate of glutamate production extrapolated to infinite alpha-methylisocitrate concentration was about 60% of the uninhibited rate.
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PMID:Activities of NAD-specific and NADP-specific isocitrate dehydrogenases in rat-liver mitochondria. Studies with D-threo-alpha-methylisocitrate. 3 61

At 0-3 days of age the plasma ammonium concentration in full term appropriate for gestational age (AGA) infants was (mean +/- SEM) 27.5 +/- 0.5 micron; a value similar to that reported in adults. Ammonium levels in low birthweight AGA and SGA groups were 47.0 +/- 2.0 micron and 45.1 +/- 3.3 micron respectively; significantly elevated (P less than 0.001) as compared to the full term group. These increased ammonium levels persisted at 3-5 weeks of age. Associated with the hyperammonemia was a significant (P less than 0.01) decrease in plasma alpha-ketoglutarate concentration: 11.8 +/- 1.0 micron, in the low birthweight AGA as compared to 20.7 +/- 0.6 micron in the full term AGA infants. There was an inverse linear correlation between plasma concentrations of ammonium and alpha-ketoglutarate r = -0.86, P less than 0.001. Urinary orotate excretion was significantly elevated (P less than 0.05) in low birthweight AGA infants. There was no difference in the plasma concentrations of glutamine, glutamate, or alanine among the various groups. Hyperammonemia was not associated with neurologic dysfunction.
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PMID:Asymptomatic hyperammonemia in low birthweight infants. 64 93

The effects of chronic hyperammonemia on cerebral metabolism were studied in rats four and eight weeks after the construction of a portacaval shunt. Compared to sham-operated controls, shunted animals had increased arterial concentrations of ammonia and glutamine and decreased glutamate. Cerebral blood flow, measured by xenon 133 washout in animals lightly anesthetized with nitrous oxide, increased from a control of 91 +/- 5 (mean +/- SEM) to 139 +/- 20 ml per 100 gm tissue per minute after shunting for eight weeks; however, the cerebral metabolic rate for oxygen was not different from control four or eight weeks after the shunting procedure. Following intraperitoneal administration of a small ammonium acetate load (2.6 mmol/kg), eight-week portacaval animals consistently underwent a fall in cerebral blood flow and cerebral oxygen consumption and developed high-voltage slow waves in the electroencephalogram. Glutamine was produced by the brains of all groups of animals; the cerebral metabolic rate for glutamine was greater than control in eight-week portacaval rats, the only animals to show a net uptake of ammonia into brain. The findings suggest that increased cerebral sensitivity to ammonia, along with nonspecific effects of chronic portal-systemic shunting, may lead to uncoupling of cerebral blood flow and oxidative metabolism.
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PMID:Cerebral blood flow and metabolism in chronically hyperammonemic rats: effect of an acute ammonia challenge. 66 74

Stria vascularis from guinea pig cochleae was incubated in vitro to determine its metabolic response to variations in substrate and ion composition of the incubation medium. The respiratory rate at 37 degrees C in a medium containing glucose and pyruvate as substrate was 17.3 +/- 1.33 (SEM, n = 51) microliter O2/mg dry weight-hour. The stria could not maintain constant respiration by relying solely upon endogenous fuel stores. With substrate supplied, the ATP level could be maintained at about 73% of that existing in vivo. Glucose appears to be an adequate substrate for stria in vitro since glutamate, pyruvate, and fumarate did not increase the respiratory rate. Succinate increased respiration markedly but did not increase the ATP level. Ouabain (10(-4) M) caused a 48% decrease in the respiratory rate. Incubation in Na+-free and K"-free medium, each resulted in irreversible decrease of respiratory rate comparable to (or greater than) that caused by ouabain. These data are in accord with the high activity of Na+-K+-ATPase in the stria and the pronounced sensitivity of the endolymphatic potential to ouabain.
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PMID:Respiratory rate and ATP content of stria vascularis of guinea pig in vitro. 71 73

Although isoflurane is a known cerebral vasodilator, the mechanism of isoflurane-induced vasodilation is not clear. The purpose of this study was to investigate the effects of 2.6% isoflurane (1.2 mM) on macroscopic calcium and potassium channel currents in voltage-clamped canine middle cerebral artery cells. Cells were dialyzed with K(+)-glutamate solution and superfused with Tyrode's solution for measurement of potassium current (n = 20). Stepwise depolarization from a holding potential of -60 mV to beyond -30 mV elicited an outward, slowly inactivating potassium current that was reduced 50% +/- 2% and 81% +/- 3% (mean +/- SEM) in the presence of 1 mM 4-aminopyridine and 30 mM tetraethylammonium, respectively. Calcium ionophore (A23187, 10 microM) increased the potassium current by 76% +/- 3%, suggesting calcium dependency. Isoflurane reduced the amplitude of the potassium current by 35% +/- 4%. Calcium current was measured in cells dialyzed with solution containing 130 mM Cs(+)-glutamate and superfused with solution containing 10 mM BaCl2 and 135 mM tetraethylammonium to pharmacologically isolate the calcium current (n = 13). Under these conditions, progressive depolarizing steps from -60 mV elicited an inward current that was maximally activated at +20 mV and essentially eliminated by 1 microM nifedipine. This current, resembling a long-lasting (L-type) Ca2+ channel current, was reduced 40% +/- 4% by isoflurane. The results of this study suggest that isoflurane acts directly at the vascular muscle membrane to suppress transmembrane calcium and potassium currents. The decrease in calcium current would cause vasodilation; however, the concomitant decrease in potassium current may partially antagonize the depressant effect of isoflurane mediated through calcium current reduction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of isoflurane on K+ and Ca2+ conductance in isolated smooth muscle cells of canine cerebral arteries. 132 7

A hair cell (octavolateralis mechanoreceptor cell) sheet preparation from the trout saccular macula was superfused with bicarbonate-based physiological saline. Among the primary amine-containing compounds resolved by cation-exchange HPLC, glutamate alone was released in a statistically significant manner with elevation of extracellular [K+] from 3.5 to 14 mM in the presence of 1.8 mM calcium. Release of glutamate averaged 10.9 +/- 2.5 pmol (mean +/- SEM) over a 10-min period for a hair cell sheet preparation representing 20 micrograms of cell protein. No potassium-evoked release of glutamate was observed in 0 mM calcium/10 mM magnesium saline, suggesting calcium dependency. Because the sheet preparation, by the method of its isolation, contained only the hair cell as the intact cell type, release of glutamate, induced by relatively small increases in extracellular potassium, can be attributed directly to the receptor cell. The specific release of glutamate and its block by magnesium are consistent with the hypothesis that glutamate is one neurotransmitter/neuromodulator mediating receptoneural transmission in the octavolateralis periphery.
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PMID:Glutamate, of the endogenous primary alpha-amino acids, is specifically released from hair cells by elevated extracellular potassium. 135 33

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

In immature rodent brain, the glutamate receptor agonist N-methyl-D-aspartate (NMDA) is a potent neurotoxin. In postnatal day (PND)-7 rats, intrastriatal injection of 25 nmol of NMDA results in extensive ipsilateral forebrain injury. In this study, we examined alterations in high-affinity [3H]glutamate uptake (HAGU) in NMDA-lesioned striatum. HAGU was assayed in synaptosomes, prepared from lesioned striatum, the corresponding contralateral striatum, or unlesioned controls. Twenty-four hours after NMDA injection (25 nmol), HAGU declined 44 +/- 8% in lesioned tissue, compared with the contralateral striatum (mean +/- SEM, n = 6 assays, p less than 0.006, paired t test). Doses of 5-25 nmol of NMDA resulted in increasing suppression of HAGU (5 nmol, n = 3; 12.5 nmol, n = 3; and 25 nmol, n = 5 assays; p less than 0.01, regression analysis). The temporal evolution of HAGU suppression was biphasic. There was an early transient suppression of HAGU (-28 +/- 4% at 1 h; p less than 0.03, analysis of variance, comparing changes at 0.5, 1, 2, and 3 h after lesioning); 1 or 5 days postinjury there was sustained loss of HAGU (at 5 days, -56 +/- 11%, n = 3, p less than 0.03, paired t test, lesioned versus contralateral striata).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Excitotoxic brain injury suppresses striatal high-affinity glutamate uptake in perinatal rats. 167 87

Successful long-term myocardial preservation is dependent on optimizing conditions during arrest, storage, and reperfusion. Neonatal piglet hearts were arrested and stored in University of Wisconsin solution (UW) at 4 degrees C for 24 hours and reperfused on a blood-perfused, adult animal-supported isolated circuit. Results were compared with nonischemic continuously perfused control hearts (group 1, n = 5). The initial 10 minutes of reperfusion in groups 2-4 was modified by aspartate/glutamate-enriched leukocyte-depleted blood cardioplegia (group 2, n = 7), leukocyte depletion alone (group 3, n = 9), and aspartate/glutamate-enriched blood cardioplegia alone (group 4, n = 6). After 10 minutes, perfusion was continued with unmodified whole blood. In group 5 (n = 9), unmodified whole blood was used for initial reperfusion as well as subsequent perfusion. The stroke work index was determined 60 minutes after reperfusion. Biopsies for high-energy phosphates, myocardial water content, and electron microscopy were obtained after functional assessment. The stroke work index at left ventricular end-diastolic pressure of 9 mm Hg did not differ between groups 1 and 2 (19.0 +/- 1.4 x 10(3) and 19.0 +/- 1.5 x 10(3) [mean +/- SEM] erg/g, respectively). These were both different from group 5 (13.3 +/- 0.8 x 10(3) erg/g, p less than 0.05). Group 3 showed improved function (15.7 +/- 0.7 x 10(3) erg/g), but this did not reach statistical significance when compared with group 5. No difference was found between groups 4 and 5. Myocardial water content, high-energy phosphate levels, and ultrastructure were similar in all groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Complete functional recovery after 24-hour heart preservation with University of Wisconsin solution and modified reperfusion. 168 70

Adult rats treated neonatally with monosodium glutamate (MSG) exhibit lesions in the arcuate nucleus of the hypothalamus. Following MSG lesioning, dopamine content in median eminence/arcuate nucleus (ME/AN) tissue extracts declined by 60-70%. Substance P (SP) content as determined by radioimmunoassay was significantly decreased in the paraventricular nucleus (PVN) (531 +/- 30 pg, mean +/- SEM) compared to controls (871 +/- 110 pg) but was unchanged in ME/AN extracts. Substance K (SK) content decreased to 257 +/- 20 pg in the PVN of lesioned animals compared to controls (367 +/- 31 pg) and the ME/AN content of SK was also significantly decreased (236 +/- 36 pg compared to control levels of 619 +/- 65 pg). The CRF-41 content of the PVN and ME/AN was unchanged by MSG lesioning, indicating that these areas are not affected by MSG. The partial depletion of SP and SK in the PVN following MSG treatment provides evidence that at least some of the neurokinin content of the PVN may originate in cell bodies of the arcuate nucleus. However, the lack of response of ME/AN SP to MSG treatment may suggest that the arcuate nucleus is not the major source of SP in the median eminence.
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PMID:Substance P and substance K in the rat hypothalamus following monosodium glutamate lesions of the arcuate nucleus. 171 32


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