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At least 1,243 records · Page 69Linked to original sources
PubMed1990

Possible mechanism of vasogenic brain oedema induced by arachidonic acid.

Free arachidonic acid was infused into normal rat brains and the effect of arachidonic acid on capillary permeability was investigated by measuring the regional uptake of 14C-aminoisobutyric acid with a quantitative autoradiographic method. Arachidonic acid increased capillary permeability in a dose-dependent manner up to 2 mM. A high dose of arachidonic acid (greater than 5 mM) produced a profound tissue destruction around the needle track and less increased capillary permeability than 2 mM arachidonic acid. Time-course study disclosed that arachidonic acid markedly increased capillary permeability within 2 hours after infusion, and continued to increase with time to 24 hours. The effect of 48 hours infusion was about a half of that at 24 hours, indicating that the effect of arachidonic acid was partially reversible. Pretreatment with dexamethasone significantly inhibited the arachidonic acid-induced increase in capillary permeability and the administration of actinomycin D 1 hour before the pretreatment with dexamethasone suppressed the inhibitory effect of dexamethasone. These results suggest that arachidonic acid, which is deposited in the extracellular space, increases brain capillary permeability by two different ways. One is the direct detergent effect of arachidonic acid, and the other is the effect of arachidonic acid that is released from the membrane by the activation of phospholipase A2.

Animals↗
PubMed1993

Relationship between amino acid transport and protein synthesis in rat isolated pancreatic acini under stimulation with cholecystokinin.

The effects of cholecystokinin octapeptide (CCK8) on amino acid transport and protein synthesis in the pancreatic acini were determined. The question of whether those effects differed between amino acid transport systems A and L was also investigated. The influx of alpha-[3H]aminoisobutyric acid (AIB, system A) and [14C]cycloleucine (system L) into isolated rat pancreatic acini and the incorporation of [14C]alanine (system A) and [3H]leucine (system L) into trichloroacetic acid (TCA)-precipitable protein in pancreatic acini were studied in the presence of various concentrations of CCK8. CCK inhibited the amino acid transport across the basolateral membrane of pancreatic acini. This effect was mediated by Ca2+, and was more responsive to amino acid transport system L than to A. CCK also inhibited protein synthesis in pancreatic acini in a dose-dependent manner. The inhibition of protein synthesis by CCK was thought to be mainly due to the inhibition of amino acid transport by CCK. Therefore, the predominant utilization of extracellular amino acids in protein synthesis was suggested.

Alanine↗
PubMed1983

Blood-brain barrier permeability to dipeptides and their constituent amino acids.

The penetration of two [14C]-labelled dipeptides, glycyl-L-phenylalanine and glycyl-L-leucine, and of their constituent amino acids into the brain of the rat was measured employing an intracarotid injection technique. The brain-uptakes of the dipeptides were about equal to that of sucrose suggesting a negligible extraction from the blood during the 15-s period of exposure to the peptides. Brain uptakes for L-phenylalanine and L-leucine were large and in agreement with earlier work on these amino acids; self-inhibition by unlabelled amino acids was marked as also inhibition by the typical L-transport system substrate, 2-aminobicyclo (2, 2, 1) heptane-2 carboxylic acid (BCH), whilst the substrate for the A-system, N-methyl-L-aminoisobutyric acid (MeAIB) was without effect. Uptake of L-phenylalanine and L-leucine was not inhibited by dipeptides in 10 mM concentration. The uptakes of [14C]-labelled MeAIB and glycine were not significantly different from that of sucrose. It is concluded that peptide formation effectively excludes the rapidly penetrating L-system amino acids, L-leucine and L-phenylalanine, from access to the L-system channel.

Amino Acids↗
PubMed1996

Volume regulation and the efflux of amino acids from cells in incubated slices of rat cerebral cortex. II. Dependence on Ca2+ ions.

The efflux of gamma-aminoisobutyric acid (GABA) and L-glutamate from pre-loaded cells in rat cerebral cortical slices has been studied during interventions designed to affect the availability of intracellular Ca2+ during hyposmotic swelling and membrane depolarization due to raised extracellular K+. Calmodulin-dependent acceleration of amino acid efflux in hyposmotic media, with cell swelling less than would be predicted on the basis of perfect osmometric behaviour (see Ref. [1]), was unaffected by Ca-ionophore in the presence of external Ca2+ or by the omission of external Ca2+, but was suppressed by pre-exposure of slices to thapsigargin (2 microM), which is reported to deplete cytosolic Ca2+, and by TMB-8 (0.5 mM), which blocks release of Ca2+ from internal stores. TMB-8 also led to significant cell swelling. The effects of TMB-8 were reversed by Ca-ionophore. Raised external K+ (54 mM) led to accelerated amino acid efflux which required calmodulin activation and was blocked by (i) omission of external Ca2+, (ii) the voltage-sensitive Ca2+ channel blocker nifedipine (1 microM), (iii) the anion transport inhibitor DIDS (25 microM for GABA, 100 microM for L-glutamate, see Ref. [1]), and (iv) the -SH group acetylator N-ethylmaleimide. TMB-8 was without effect in high K+ media. These results suggest that while enhanced amino acids efflux probably occurs through the same population of Ca/calmodulin-dependent, DIDS-sensitive pathways following hyposmotic shock or membrane depolarization, the source of Ca2+ ions required for the activation of these pathways may depend upon which of these acceleratory stimuli is applied.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1991

Molecular size of a Na(+)-dependent amino acid transporter in Ehrlich ascites cell plasma membranes estimated by radiation inactivation.

Radiation inactivation was used to estimate the molecular size of a Na(+)-dependent amino acid transport system in Ehrlich ascites cell plasma membrane vesicles. Na(+)-dependent alpha-aminoisobutyric acid uptake was measured after membranes were irradiated at -78.5 degrees C in a cryoprotective medium. Twenty-five percent of the transport activity was lost at low radiation doses (less than 0.5 Mrad), suggesting the presence of a high molecular weight transport complex. The remaining activity (approximately 75% of total) decreased exponentially with increasing radiation dose, and a molecular size of 347 kDa was calculated for the latter carrier system. Vesicle permeability and intravesicular volume were measured to verify that losses in transport activity were due to a direct effect of radiation on the transporter and not through indirect effects on the structural integrity of membrane vesicles. Radiation doses 2-3-fold higher than those required to inactivate amino acid transport were needed to cause significant volume changes (greater than 15%). Vesicle permeability was unchanged by the irradiation. The structural integrity of plasma membrane vesicles was therefore maintained at radiation doses where there was a dramatic decrease in amino acid transport. The relationship between the fragmentation of a 120-130-kDa peptide, a putative component of the Na(+)-dependent amino acid carrier [McCormick, J. I., & Johnstone, R. M. (1988) Proc. Natl. Acad. Sci. U.S.A. 85, 7877-7881], and loss of transport activity in irradiated membranes was also examined. Peptide loss was quantitated by Western blot analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Transport Systems↗
PubMed1985

A highly active chemotactic peptide analog incorporating the unusual residue 1-aminocyclohexanecarboxylic acid at position 2.

Analogs of chemotactic peptides (Formyl-Met-X-Phe-OMe) containing the stereochemically constrained residues alpha-aminoisobutyric acid (Aib), 1-aminocyclopentanecarboxylic acid (Acc5) and 1-aminocyclohexanecarboxylic acid (Acc6) at position 2 are compared with the parent sequence (X = Leu) for their ability to induce lysozyme release in rabbit neutrophils. The Acc6 analog is about 78 times more active than the parent peptide, For-Met-Leu-Phe-OH, whereas Aib and Acc5 analogs are approximately 3 and 2 times, respectively, less active than the parent peptide. NMR and model building studies clearly favour a Met-Acc6 beta-turn solution conformation in the Acc6 analog, suggesting that the neutrophil receptor is capable of recognizing a folded peptide structure. The significant differences in the activities of the Acc5 and Acc6 analogs suggest an important role for the residue 2 sidechain in receptor interactions.

Amino Acids↗
PubMed1986

Regulation of amino acid uptake by phorbol esters and hypertonic solutions in rat thymocytes.

Growth factors, mitogens, and malignant transformation can alter the rate of amino acid uptake in mammalian cells. It has been suggested that the effects of these stimuli on proliferation are mediated by activation of Na+/H+ exchange. In lymphocytes, Na+/H+ exchange can also be activated by phorbol esters and by hypertonic media. To determine the relationship between the cation antiport and amino acid transport, we tested the effects of these agents on the uptake of alpha-aminoisobutyric acid (AIB), methyl-AIB, proline, and leucine in rat thymocytes. Both 12-O-tetradecanoylphorbol-13-acetate (TPA) and hypertonicity stimulated amino acid uptake through system A (AIB, proline, and methyl-AIB). In addition, TPA, but not hypertonicity, also elevated leucine uptake. The stimulation of the Na+ -dependent system A was not due to an increased inward electrochemical Na+ gradient. The effects of TPA and hypertonic treatment were not identical: Stimulation of AIB uptake by TPA was observed within minutes, whereas at least 1 hr was required for the effect of hypertonicity to become noticeable. Moreover, stimulation by hypertonicity but not that by TPA, was partially inhibited by cycloheximide, suggesting a role of protein synthesis. That stimulation of Na+/H+ exchange does not mediate the effects on amino acid transport is suggested by two findings: 1) the stimulation of AIB uptake was not prevented by concentrations of amiloride or of 5-(N,N-disubstituted) amiloride analogs that completely inhibit the Na+/H+ antiport and 2) conditions that mimic the effect of the antiport, namely, increasing [Na+]i or raising pHi failed to stimulate amino acid uptake. Thus, in lymphocytes, activation of Na+/H+ exchange and stimulation of amino acid transport are not casually related.

Amino Acids↗
PubMed1990

Effect of catabolic hormone infusion on protein turnover and amino acid uptake in skeletal muscle.

Increased plasma levels of the catabolic hormones glucagon, epinephrine, and cortisol have been implicated in mediating various metabolic alterations in trauma and sepsis. Their role in altered protein turnover and amino acid transport in skeletal muscle during sepsis, however, is not known. In the current study, rats were infused with a mixture of the catabolic hormones for 16 hours. Control animals were infused with vehicle solution. Protein synthesis and degradation rates were measured in incubated, intact soleus muscles as incorporation of 14C-phenylalanine into protein and release of tyrosine into incubation medium, respectively. Muscle amino acid uptake was determined by measuring the intracellular to extracellular ratio of [3H]-alpha-aminoisobutyric acid after incubation for 2 hours. Infusion of catabolic hormones for 16 hours resulted in elevated plasma glucose and lactate levels, reduced plasma concentrations of most amino acids, and accelerated muscle protein breakdown, similar to previous findings in septic rats. Protein synthesis rates and amino acid uptake in incubated muscles were not significantly different in control and hormone-infused rats. The current study suggests that increased muscle proteolysis in sepsis and severe injury may be mediated in part by catabolic hormones. In contrast, reduced muscle protein synthesis and amino acid uptake are probably signaled by other substances or mechanisms.

Amino Acids↗
PubMed2005

Differential regulation of amino acid transporter SNAT3 by insulin in hepatocytes.

The liver is a metabolism and transfer center of amino acids as well as the prime target organ of insulin. In this report, we characterized the regulation of system N/A transporter 3 (SNAT3) in the liver of dietary-restricted mice and in hepatocytes treated with serum starvation and insulin. The expression of SNAT3 was up-regulated in dietary-restricted mice. The expression of SNAT3 protein was detected on the plasma membrane of hepatocyte-like H2.35 cells with a half-life of 6-8 h. When H2.35 cells were depleted of serum, the expression of SNAT3 was increased. An increased concentration of insulin, however, suppressed SNAT3 expression. Interestingly, the down-regulation of SNAT3 expression by insulin was blocked by the specific phosphoinositide 3-kinase inhibitor LY294002 and mammalian target of rapamycin inhibitor, but not by MAPK inhibitor PD98059, suggesting that insulin exerts its effect on SNAT3 through phosphoinositide 3-kinase-mammalian target of rapamycin signaling. Surface biotinylation assay showed an increased level of SNAT3 on the cell surface after 0.5 h of insulin treatment, although no effect was observed after 24 h of treatment. Consistently, the transport of the substrate l-histidine was increased with short, but not long, treatment by insulin in both H2.35- and SNAT3-transfected COS-7 cells. The L-histidine uptake was inhibited significantly by L-histidine followed by 2-endoamino-bicycloheptane-2-carboxylic acid and L-cysteine and to a lesser extent by L-alanine and aminoisobutyric acid, but was not inhibited by alpha-(methylamino)isobutyric acid, implying that uptake of L-histidine in H2.35 cells is primarily mediated by system N transporters. In conclusion, differential regulation of SNAT3 by insulin and serum starvation reinforces the functional significance of this transporter in liver physiology.

Amino Acid Transport Systems, Neutral↗
PubMed1994

The role of platelet-activating factor in alterations of system A amino acid transport in rat soleus and extensor digitorum longus muscles during endotoxic shock.

We investigated the role of platelet-activating factor (PAF) as a mediator of system A amino acid transport alterations in skeletal muscle during endotoxic shock. Male Sprague-Dawley rats (80-100 g) were injected with Salmonella enteritidis endotoxin (10 mg/kg intravenously (i.v.)) or PAF (4 micrograms/kg i.v.) and killed 5 or 1 h later, respectively. Control rats were injected with a vehicle. System A amino acid transport was assessed by measuring the cellular uptake of 1-14C-alpha-aminoisobutyric acid (AIB, amino acid analog) in isolated soleus and extensor digitorum longus (EDL) muscles, in vitro. AIB uptake in soleus and EDL from endotoxic rats was approximately 33% lower than control muscles. The i.v. injection of PAF reduced AIB uptake 9% in soleus and 15% in EDL as compared with muscles from control rats. The prophylactic administration of WEB 2086 (30 mg/kg i.v.), a PAF receptor antagonist, attenuated the endotoxin-induced inhibition of amino acid transport by 26% in EDL and 17% in soleus. PAF (1 microgram/mL) added to incubation media had no effect on AIB uptake in soleus and EDL of control rats. However, there was a reduction in AIB uptake in soleus and EDL obtained from rats 1 h after an i.v. injection of PAF (4 micrograms/kg) and after incubation in media containing PAF (1 microgram/mL). Addition of plasma to incubation media obtained from rats 1 h after the i.v. injection of endotoxin or PAF attenuated AIB uptake in soleus and EDL of control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed1984

Effects of static and cyclic compressive loading on articular cartilage plugs in vitro.

The influence of static and intermittent stress on articular cartilage metabolism was examined in vitro. Full-thickness plugs of cartilage from femoral condyles of normal adult dogs were cultured while static or cyclic stresses were applied for 2 hours. The plugs were then incubated under atmospheric pressure for 2 hours in medium containing radioactive label, to provide measurements of net synthesis of glycosaminoglycan (GAG) or protein. As a control, cartilage from the same knee was cultured in the apparatus at atmospheric pressure. When cartilage plugs were exposed to static stress, or to cyclic stresses at a duty cycle of 60 seconds on/60 seconds off, net GAG synthesis was suppressed to 30-60% of that in controls. In contrast, when a duty cycle of 4 seconds on/11 seconds off was used, GAG synthesis was increased by 34%. The duty cycle which increased GAG synthesis did not affect protein synthesis or tissue contents of DNA, uronic acid, or water. At the cycle which suppressed GAG synthesis, protein synthesis and uronic acid content were decreased, and water content was increased. As judged by uptake of 14C-aminoisobutyric acid and 14C-xylose, the above changes in GAG synthesis do not appear to have been due to changes in diffusion of nutrient molecules through the cartilage during loading.

Animals↗
PubMed1978

Glutamine and glutamic acid uptake by rat renal brushborder membrane vesicles.

Glutamine uptake by rat renal brushborder vesicles occurred via two distinct saturable processes with Km values of 0.145 and 8.5 mM which were stimulated by both ionic and sodium gradients with a pH optimum of 6.8--7.1. Glutamic acid uptake also occurred by a two-component system with Km values of 0.016 and 3.60 mM. Both components were stimulated specifically by a sodium gradient. The low Km system for glutamic acid had a pH optimum of 7.2--7.4. Glutamine entry at 0.06 mM was inhibited by a variety of amino acids at 3 mM, including dibasic amino acids, glycine, valine, and phenylalanine. Glutamic acid entry at 0.06 mM was inhibited 20--30% by 3 mM phenylalanine, valine, alpha-aminoisobutyric acid, and glutamine. No metabolic alteration of glutamic acid was observed on incubation with membrane vesicles, but glutamine was significantly hydrolyzed to glutamic acid upon prolonged incubation. Hydrolysis of glutamine was negligible at 15 sec incubation which was employed for measurement of initial rate of entry. These studies provide support for the existence of an uptake system in the brushborder of the renal proximal tubule cell capable of handling the reabsorption of glutamine normally present in glomerular filtrate.

Amino Acids↗
PubMed1977

Specificity of trans-inhibition of amino acid transport in baker's yeast.

The trans-inhibition potency of intracellular amino acids on the transport of various amino acids follows the same sequence, viz. Pro(Lys), Phe, Glu, Ala, Gly, Leu, and alpha-aminoisobutyric acid. The same sequence was found for the reciprocal of trans-inhibition constants. It appears that the intracellular amino acid itself or a derivative thereof acts on a component that is common to all amino acid transport systems of baker's yeast.

Amino Acids↗
PubMed1988

Bisfunction of propionic acid on purified rat liver beta-ureidopropionase.

Propionic acid and isobutyric acid, which are structural analogues of N-carbamoyl-beta-alanine and N-carbamoyl-beta-aminoisobutyric acid, respectively, acted as an allosteric activator as well as a competitive inhibitor of purified rat liver beta-ureidopropionase. Propionic acid and isobutyric acid had a Ki value of approx. 0.3 mM at pH 7.0. The Hill coefficient for N-carbamoyl-beta-alanine was 2.0, but the cooperatively decreased to 1.0 in the presence of 1 mM propionic acid. The K1/2 value towards N-carbamoyl-beta-alanine was calculated to be 0.17 mM from Hill plots and the Km value was determined to be 0.06 mM from replots of the apparent Km vs propionic acid.

Amidohydrolases↗
PubMed1981

Role of induced proteins in insulin-stimulated sodium transport.

Insulin increases active sodium transport by the toad urinary bladder, an effect that begins with 15 minutes and persists for at least 20 hours. Although pretreatment of bladders with inhibitors of RNA or protein synthesis has no effect on the response to insulin within the first hour, these agents block the long-term component of insulin-stimulated sodium transport. To examine the relationship of protein synthesis to the sustained increase in sodium transport elicited by insulin, we have studied the effects of the hormone upon the incorporation of radioactive amino acids into mucosal cell proteins. There is no detectable effect of insulin on the uptake of aminoisobutyric acid into mucosal cells or on the incorporation of labeled precursors into total protein; however, using a dual-label technique, we find that insulin increases the incorporation of amino acids into specific soluble and plasma-membrane proteins of granular mucosal cells. Insulin has no discernible effect upon the incorporation of amino acids into proteins of mitochondria-rich mucosal cells. Thus the effects of insulin upon sodium transport appear to be the result of two separate mechanisms, (1) a short-term response that is independent of protein synthesis and (2) a long-term response that is expressed after the first hour of hormone treatment and that requires the synthesis of one or more specific proteins in the granular cell.

Amino Acids↗
PubMed1989

Effect of chronic vanadate ingestion on amino acid and water absorption in rat intestine.

Chronic administration of a relatively low concentration of vanadate to rats causes inhibition of water, alpha-aminoisobutyric acid (AIB) and L-alanine absorption. The mechanism responsible for this inhibition was tested by studying the uptake of alanine in isolated rat intestinal cells. The studies suggest that the vanadate inhibition of amino acid transport is primarily caused by a decreased activity of the Na+-K+ pump, an action that is similar to what is observed when the rat intestine is acutely exposed to vanadate. Vanadate appeared to have no direct effect on the entry of amino acids into the intestinal cell. This was evident by the fact that amino acid uptake by enterocytes of control rats was not different from the uptake by cells of vanadate-treated animals that have an inwardly directed Na gradient artificially created across them. Furthermore, 86RB influx and efflux into and out of intestinal tissues of the vanadate-treated animals were, respectively, decreased and increased as compared to normal control tissues and they were similar to what is observed when the intestine is acutely exposed to ouabain, a known specific inhibitor of the Na+-K+ pump.

Amino Acids↗
PubMedDate not supplied

Total synthesis of zervamicin IIB and its deuterium-labelled analogues.

For the first time the total synthesis of the peptaibol zervamicin IIB is described. Synthesis of this peptaibol was achieved by the Fmoc/tert-butyl strategy in solution using a fragment condensation approach. Three fragments of zervamicin IIB were obtained by stepwise elongation with Fmoc amino acids using BOP as a coupling reagent. For the introduction of the highly sterically hindered alpha-aminoisobutyric acid residues BOP/DMAP activation was applied. The fmoc group was removed by reaction with 0.1 M NaOH in dioxane/methanol/water (30/9/1, v/v/v). Peptide fragments were coupled by means of a new coupling reagent, CF3-PyBOP. Using the strategy developed, zervamicin IIB and two analogues specifically deuterium-labelled at different positions of the glutamine-11 residue have been synthesized in 40% overall yield based on the isotopically labelled amino acid and with 98 +/- 2% of isotope enrichment. FAB mass spectroscopy, 600 MHz 1H-NMR spectroscopy and high-performance liquid chromatography provided convincing evidence that the synthetic products, zervamicin IIB and its deuterium-labelled analogues, fully correspond to the naturally occurring zervamicin IIB.

Amino Acid Sequence↗