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

The exchange of intramitochondrial ATP (ATP(in)) for extramitochondrial ATP (ATP(out)) was measured by using 31P NMR spectroscopy over a range of temperatures in isolated rat liver mitochondria oxidizing glutamate and succinate in the presence of external ATP but no added ADP (state 4). The rate of this exchange is more than an order of magnitude faster than rates reported previously that were determined by using isotopic techniques in the presence of oligomycin, the potent ATPase inhibitor. Differences are ascribed in part to the low levels of matrix ATP present in oligomycin-treated mitochondria. The addition of oligomycin to mitochondrial suspensions decreases intramitochondrial ATP levels from 17 +/- 3 (SEM) nmol/mg of protein in state 4 to 1.51 +/- 0.1 nmol/mg of protein in the presence of inhibitor at 8 degrees C. Simultaneously, transporter flux falls from 960 +/- 55 nmol/min.mg to undetectable levels (less than 300 nmol/min.mg). Although transport rates are much faster when measured by saturation-transfer than by conventional isotopic methods, the enthalpy values obtained by determining the effect of temperature on flux are very similar to those reported in the past that were determined by using isotopic techniques. Intramitochondrial ATP content regulates the rate of the ATP(in)/ATP(out) exchange. At 18 degrees C, the concentration of internal ATP that produces half-maximal transport rate is 6.6 +/- 0.12 nmol/mg of mitochondrial protein. The relationship between substrate concentration and flux is sigmoidal and is 90% saturated at 11.3 +/- 0.18 nmol/mg of mitochondrial protein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:31P NMR saturation-transfer study of the in situ kinetics of the mitochondrial adenine nucleotide translocase. 188 22

The objectives of our experiments were 1) to determine the effect of N-methyl-D,L-aspartate (NMA), an agonist of the neuroexcitatory amino acids aspartate and glutamate, on growth hormone (GH) release in ovariectomized ewes, and 2) to determine the effect of naloxone, an opioid antagonist, on the GH response to NMA. Jugular blood was collected via venipuncture at 12-min intervals for 2 h before and 2 h after i.v. injection of NMA. In Exp. 1, ewes received either 0, 6, 12 or 24 mg NMA/kg BW dissolved in .9% saline solution (n = 4 per treatment). Growth hormone concentrations were similar (P greater than .1) between groups prior to injection (9.8 +/- .7 ng/ml; mean +/- SEM) and were unaffected (P greater than .1) by saline treatment. In contrast, 6, 12 or 24 mg NMA/kg BW increased mean GH concentration by 210% (P less than .04), 273% (P less than .02) and 234% (P less than .02), respectively. In Exp. 2, ewes received NMA (6 mg/kg BW) 5 min after either saline (n = 4) or naloxone (1 mg/kg BW; n = 4) pretreatment. Serum GH concentrations averaged 7.0 +/- 1.1 ng/ml before pretreatment and increased similarly (238%; P greater than .1) in both groups following NMA. In summary, NMA increased GH concentrations in ovariectomized ewes by some mechanism that does not involve opioid receptors that are antagonized by naloxone.
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PMID:Growth hormone release after N-methyl-D,L-aspartate in sheep: dose response and effect of an opioid antagonist. 225 96

Acute liver failure was induced in rats by a single intragastric dose of carbon tetrachloride. This causes hepatic centrilobular necrosis, as indicated by histological examinations, and produces a large increase in the activity of serum alanine aminotransferase. The plasma NH4+ level (mean +/- SEM) was 123 +/- 10 microM in the control group and 564 +/- 41 microM in animals with acute liver failure (each n = 5). 31P nuclear magnetic resonance (NMR) was used to monitor brain cortical high-energy phosphate compounds, Pi, and intracellular pH. 1H NMR spectroscopy was utilised to detect additional metabolites, including glutamate, glutamine, and lactate. The results show that the forebrain is capable of maintaining normal phosphorus energy metabolite ratios and intracellular pH despite the metabolic challenge by an elevated blood NH4+ level. There was a significant increase in the brain glutamine level and a concomitant decrease in the glutamate level during hyperammonaemia. The brain lactate level increased twofold in rats with acute liver failure. The results indicate that 1H NMR can be used to detect cerebral metabolic changes in this model of hyperammonaemia, and our observations are discussed in relation to compartmentation of NH4+ metabolism.
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PMID:Observation of cerebral metabolites in an animal model of acute liver failure in vivo: a 1H and 31P nuclear magnetic resonance study. 235 29

In an experimental model of perinatal hypoxic-ischemic brain injury, we examined quisqualic acid (Quis)-stimulated phosphoinositide (PPI) turnover in hippocampus and striatum. To produce a unilateral forebrain lesion in 7-day-old rat pups, the right carotid artery was ligated and animals were then exposed to moderate hypoxia (8% oxygen) for 2.5 h. Pups were killed 24 h later and Quis-stimulated PPI turnover was assayed in tissue slices obtained from hippocampus and striatum, target regions for hypoxic-ischemic injury. The glutamate agonist Quis (10(-4) M) preferentially stimulated PPI hydrolysis in injured brain. In hippocampal slices of tissue derived from the right cerebral hemisphere, the addition of Quis stimulated accumulation of inositol phosphates by more than ninefold (1,053 +/- 237% of basal, mean +/- SEM, n = 9). In contrast, the addition of Quis stimulated accumulation of inositol phosphates by about fivefold in the contralateral hemisphere (588 +/- 134%) and by about sixfold in controls (631 +/- 177%, p less than 0.005, comparison of ischemic tissue with control). In striatal tissue, the corresponding values were 801 +/- 157%, 474 +/- 89%, and 506 +/- 115% (p less than 0.05). In contrast, stimulation of PPI turnover elicited by the cholinergic agonist carbamoylcholine, (10(-4) or 10(-2) M) was unaffected by hypoxia-ischemia. The results suggest that prior exposure to hypoxia-ischemia enhances coupling of excitatory amino acid receptors to phospholipase C activity. This activation may contribute to the pathogenesis of irreversible brain injury and/or to mechanisms of recovery.
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PMID:Perinatal hypoxic-ischemic brain injury enhances quisqualic acid-stimulated phosphoinositide turnover. 283 19

Mongolian gerbils were treated with alpha-methyl-para-tyrosine methyl ester (AMPT, a tyrosine hydroxylase inhibitor), in order to decrease brain levels of catecholamines. Six hours later, unilateral ischemic stroke was induced by ligation of the left common carotid artery. The delayed degeneration of nerve terminals was studied sixteen hours later by measuring the high-affinity uptake of radiolabeled transmitters by isolated synaptosomes. Dopamine, serotonin and glutamate terminals were studied. AMPT-treated gerbils were compared to untreated (no AMPT) animals; 220 gerbils were studied. AMPT pretreatment (100, 250 and 400 mg/kg) produced a dose-dependent protection of all three types of nerve terminals. In the absence of AMPT pretreatment, the uptake of radiolabeled transmitters by the ischemic hemisphere, expressed as a percentage of that seen in the contralateral (unaffected) side of the brain, was as follows (mean +/- SEM): 27.3 +/- 5.2% for dopamine terminals, 49.5 +/- 6.2% for serotonin terminals, and 42.7 +/- 5.3% for glutamate terminals. Protection was essentially complete at a dose of 400 mg AMPT per kg. The number of animals with significant damage to nerve terminals was reduced from 38.5% in untreated animals to 11.1% in animals treated with AMPT 400 mg/kg. Although the nerve terminals were protected, gerbils still showed the behavioral signs of unilateral stroke due to the permanent occlusion of the left carotid. These results indicate that endogenous dopamine may play a significant role in ischemic damage to nerve terminals in the cerebrum.
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PMID:Nerve terminal damage in cerebral ischemia: protective effect of alpha-methyl-para-tyrosine. 286 54

gamma-Glutamyltransferase (gamma-GT) is located in the brushborder membrane of the proximal tubule where the catalytic site of the enzyme faces the lumen. The (phosphate-independent) glutaminase activity of gamma-GT in vitro is activated by hippurate. In order to investigate glutamine deamidation in the tubule lumen in vivo, 14C-L-glutamine-containing solutions were continuously microperfused through sections of the proximal convoluted tubule in vivo and in situ. D-aspartate and L-phenylalanine (10 mmol/l, each) were added to the perfusate in order keep the reabsorption of L-glutamine as such low and to block reabsorption of any glutamate possibly formed, respectively. Intraluminal formation of glutamate from glutamine in the absence of hippurate is small. In presence of 10 mmol/l hippurate, 5%-70% of the recovered 14C-activity was 14C-glutamate at an initial 14C-L-glutamine concentration of 1 mmol/l. The respective absolute rate (+/- SEM) of glutamate formation, i.e., 36 +/- 5 pmol X s-1 X m-1, was increased 1.4-fold at an initial L-glutamine concentration of 3 mmol/l, but dropped to one third at initially 0.3 mmol/l. A rough estimate of the apparent kinetic constants resulted in a Km of 0.58 (0.19-0.97) mmol/l and a Vmax of 56 (40-93) pmol X s-1 X m-1. Deamidation of glutamine occurred also in the absence of L-phenylalanine. Acivicin (AT 125), a gamma-GT inhibitor, completely blocked glutamate formation. Endogenous hippurate concentrations determined by free flow micropuncture and HPLC were 0.16 mmol/l in the late proximal convolution, 0.6 mmol/l in the early distal convolution, and 4.9 mmol/l in the final urine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ammoniagenesis catalyzed by hippurate-activated gamma-glutamyltransferase in the lumen of the proximal tubule. A microperfusion study in rat kidney in vivo. 288 Dec 49

The ingestion of monosodium glutamate in sensitive individuals has been reported to cause severe asthma. We therefore studied the effects of L-glu on airway function and histamine (H) responsiveness in the rabbit. Histamine dose response curves (HDR's) were performed by measuring total lung resistance (RL) after inhalation of saline and increasing concentrations of H (1-30 mg/ml). The concentration of H producing a 20% increase in RL (PC20H) was obtained by interpolation. To assess the effects of L-glu, 8 rabbits were infused with L-glu (0.2 g/kg/hr) or saline in random order (14 days apart) for 4 hours followed by an HDRC. To look at possible late effects, a repeat HDRC was also performed in 6 rabbits 12 hours after completion of the L-glu infusion. In order to see whether rabbits rendered hyperresponsive responded to L-glu, the above protocol was performed in 7 rabbits following the inhalation of 3 micrograms of the activated complement fragment C5a des Arg. The L-glu infusions increased the plasma levels approx. ten-fold (mean +/- SEM 0.119 +/- 0.012 base-line, 1.272 +/- 0.061 mmol/l post infusion). L-glu did not increase the PC20H or baseline RL in either the normal rabbits at 4 or 12 hours or in the C5a des Arg treated rabbits at 4 hours. It is concluded that L-glu does not cause bronchoconstriction or an increase in airway responsiveness to H in the rabbit.
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PMID:The effect of L-glutamic acid on airway function and reactivity in the rabbit. 290 65

We used intraoperative electrocorticography to identify and compare specimens from two groups of patients undergoing temporal lobectomy: (1) spiking cortex (12 patients)--epileptic activity recorded over much of the temporal convexity; and (2) nonspiking cortex (9 patients)--temporal convexity free of interictal spiking, epileptic activity confined to the hippocampus and/or amygdala. Comparative amino acid levels were (mumol/g protein, mean +/- SEM): glutamate--spiking 109.8 +/- 1.8, nonspiking 87.4 +/- 2.0 (p less than 0.001); aspartate--spiking 15.2 +/- 0.9, nonspiking 12.2 +/- 0.5 (p less than 0.05); GABA--spiking 15.0 +/- 1.0, nonspiking 13.9 +/- 1.4 (NS); taurine--spiking 14.5 +/- 0.8, nonspiking 12.2 +/- 0.8 (NS); and glycine--spiking 11.5 +/- 0.8, nonspiking 7.4 +/- 0.6 (p less than 0.01). Cortical epileptic activity appears to be associated with elevated concentrations of glutamate, aspartate, and glycine, but not GABA and taurine, perhaps indicating a relative imbalance between putative excitatory and inhibitory amino acid neurotransmitters.
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PMID:Excitatory amino acids are elevated in human epileptic cerebral cortex. 336 74

Muscle and plasma amino acids, subjective fatigue and body weight were studied in 16 patients before and 20 days after uncomplicated elective abdominal surgery. Fatigue increased from a mean (+/- SEM) preoperative level of 2.4 +/- 0.4 arbitrary units to 4.4 +/- 0.5 on postoperative day 20, while body weight fell from 67.3 +/- 2.5 to 64.7 +/- 2.9 kg (both differences p less than 0.001). Correlation was found between increase in fatigue and fall in body weight (r = 0.56, p less than 0.05). Plasma amino acids showed little change after surgery. In muscle, the nonessential amino group taurine, asparagine, glutamate and glycine increased and histidine and arginine decreased (both p less than 0.05) postoperatively. No correlation was found between postoperative fatigue and weight loss versus changes in muscle amino acids. Some of the well-defined immediate postoperative changes in muscle amino acids thus persisted into late, otherwise uncomplicated convalescence, but postoperative fatigue was related only to weight loss--not to changes in muscle or plasma amino acids.
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PMID:Fatigue and muscle amino acids during surgical convalescence. 343 98

To define alterations in myocardial mitochondrial function due to hypoperfusion, oxidative phosphorylation was simultaneously studied in 17 control (stable perfusion pressure) rat hearts and 17 hypoperfused isolated rat hearts. Hypoperfusion for 30 minutes was achieved by a reduction in coronary perfusion pressure from 77.8 +/- 1.2 mm Hg (mean +/- SEM) to 20.2 +/- 1.8 mm Hg in the experimental group (control perfusion pressure after 30 minutes 75.6 +/- 1.2). Hypoperfusion caused a reduction in left ventricular developed pressure to 20.5 +/- 1.5 mm Hg (versus control 74.8 +/- 3.3, p less than 0.0001), a reduction of coronary flow rate to 4.9 +/- 0.3 ml/min (versus control 19.4 +/- 1.2, p less than 0.0001), and a drop in myocardial oxygen consumption to 0.06 +/- 0.005 ml O2/min (versus control 0.17 +/- 0.01, p less than 0.0001). Myocardial lactate production was increased by hypoperfusion (3.0 +/- 0.6 mumol/min) compared with controls (0.7 +/- 0.5, p less than 0.02), but myocardial creatine kinase release was similar in the hypoperfused and control groups. Hypoperfusion was associated with an augmentation of state 3 mitochondrial respiration with glutamate and malate as respiratory substrates (448.8 +/- 14.0 ng atoms O/min/mg mitochondrial protein versus controls 290.7 +/- 13.4, p less than 0.001). When rates were normalized for mitochondrial malate dehydrogenase (MDHm), state 3 respiration was still increased in hypoperfused hearts (24.1 +/- 2.1 ng atoms O/min/IU MDHm) compared with controls (15.5 +/- 1.6, p less than 0.02). The rates of dinitrophenol-uncoupled electron transport were similar to the rates of state 3 respiration in both the hypoperfused and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Enhancement of mitochondrial oxidative phosphorylation capability by hypoperfusion in isolated perfused rat heart. 367 42


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