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At least 235 records · Page 13Linked to original sources
PubMed1988

Effect of dimethyl sulfoxide on blood-to-brain transfer of alpha-aminoisobutyric acid: examination of regional blood-brain barrier function.

The effect of dimethyl sulfoxide (DMSO) on brain capillary permeability has been controversial. We have studied the effect of DMSO on unidirectional transport of alpha-aminoisobutyric acid (AIB) across the blood-brain barrier (BBB) in rats. Rats were treated with 15% DMSO intraperitoneally (i.p.), intravenously (i.v.) or by an i.p. injection in combination with an i.v. injection, or in some cases intra-arterially by rapid infusion into left external carotid artery. The unidirectional blood-to-brain transfer constant (Ki) for AIB was measured in each group after the animals were killed. DMSO administration did not significantly increase Ki as compared to control Kj. These results show that it is unlikely that DMSO increases the permeability of BBB and therefore do not support the proposal that DMSO can act as a carrier at the BBB for compounds with restricted vascular permeability.

Aminoisobutyric Acids↗
PubMed1976

Uptake of alpha-aminoisobutyric acid and phosphate by membrane vesicles derived from growing and quiescent fibroblasts.

Membrane vesicles derived principally from the plasma membrane and endoplasmic reticulum of mouse 3T3 cells transformed by Simian virus 40 take up alpha-aminoisobutyric acid (AIB) and phosphate (Pi). When NaCl is added simultaneously with AIB or Pi, uptake rises two- to three-times above the equilibrium to accumulate AIB or Pi over the control value, in the presence of a Na+ gradient, is almost lost in membrane vesicles derived from benzpyrene-transformed 3T3 cells (BP3T3) arrested in the G1 phase of the cell cycle by serum starvation. When added to the membranes with NaCl and the uptake substrate, a combination of fibroblast growth factor (FGF) and epidermal growth factor EGF restores the ability of the membranes to accumulate AIB and Pi over the control value.

Aminoisobutyric Acids↗
PubMed1975

One-way fluxes of alpha-aminoisobutyric acid in Ehrlich ascites tumor cells. Trans effects and effects of sodium and potassium.

One-way fluxes in the steady state and one-way influxes at zero intracellular concentrations were measured for alpha-aminoisobutyric acid (AIB) in Ehrlich ascites tumor cells at 32 degrees C. The one-way fulxes show trans effects in the concentration of AIB and are dependent on sodium levels. The one-way fluxes for initial influx and for the steady state were fitted with the equations derived for the frequently used two-state carrier model. Estimates of the parameters of these equations were obtained with use of nonlinear least squares. These gave relatively good fits of the flux data and the data on steady-state distribution ratios. The two-state carrier model predicted a trans inhibition of one-way influx and a trans stimulation of one-way efflux. The former phenomenon has been demonstrated for AIB transport in Ehrlich ascites cells and there is evidence, through less firm, for the latter.

Aminoisobutyric Acids↗
PubMed2006

A pivotal role for beta-aminoisobutyric acid and oxidative stress in dihydropyrimidine dehydrogenase deficiency?

Dihydropyrimidine dehydrogenase (DPD) constitutes the first step of the pyrimidine degradation pathway in which the pyrimidine bases uracil and thymine are catabolised to beta-alanine and beta-aminoisobutyric acid (beta-AIB), respectively. The mean concentration of beta-AIB was approximately 5- to 8-fold lower in urine of patients with a DPD deficiency, when compared to age-matched controls. Comparable levels of 8-hydroxydeoxyguanosine (8-OHdG) were present in urine from controls and DPD patients at the age <2 year. In contrast, slightly elevated levels of 8-OHdG were detected in urine from DPD patients with an age >2 year, suggesting the presence of increased oxidative stress.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed1983

Effect of triethyl lead on the placental uptake and transfer of the non-metabolisable alpha-aminoisobutyric acid in guinea pigs.

In order to study the effect of organolead on the placental transfer of amino acids, triethyl lead chloride was administered by i.p. injections to pregnant guinea-pigs. The following day, the fetal part of the placenta was perfused in situ during i.v. infusion of alpha-aminoisobutyric acid (AIB) to the dam. It was found that triethyl lead treatment (2.5 mg/kg body wt) decreased the AIB-concentration in perfusion media compared with that of the control group. Treatment with 1 mg/kg body wt has no effect. It was also shown that the placental uptake of AIB in animals receiving 2.5 mg/kg body wt is significantly reduced compared with that of the control group. No such effect was obtained in animals receiving 1 mg/kg body wt. It is suggested that triethyl lead may inhibit placental Na+-K+-adenosinetriphosphatase, an enzyme involved with placental amino acid transport. Another possible explanation is a reduction in maternal placental blood flow.

Aminoisobutyric Acids↗
PubMed1994

A comparative study on the uptake of alpha-aminoisobutyric acid by normal and immortalized human embryonic kidney cells from proximal tubule.

We investigated whether an immortalized human kidney epithelial cell line (IHKE), compared with normal embryonic cells (NHKE), can be used as a representative system with which to characterize the transport of neutral amino acids in the proximal tubule of the human kidney. The IHKE cell line, immortalized by treatment with NiSO4, exhibited microvilli and enzyme markers specific for highly specialized tubule cells. The Na(+)-dependent uptake of alpha-aminoisobutyric acid (AIB) by IHKE and NHKE cells occurred by means of a single transport system with identical half-saturation constants, but the capacity for uptake was higher in the immortalized cells. Proton-dependent influx of AIB was also mediated by a single transport component with similar uptake characteristics in both types of cells. Imposition of an H(+)-gradient to a Na(+)-gradient reduced the sodium dependent uptake of AIB with the exception of short incubation time (1 min), where addition of a proton gradient produced a marked increase in the Na(+)-dependent influx of AIB in NHKE but not in IHKE cells. Competition experiments revealed that the Na(+)-dependent uptake at 50 microM AIB was reduced by neutral alpha-amino acids in the two cell lines. L-Glutamate, L-aspartate, L-arginine and the beta-amino acid taurine had no effect. Only in the IHKE cell line did addition of 5 mM L-lysine produce a slight inhibition. Except for L-proline all of the neutral and acidic amino acids tested reduced the H(+)-dependent uptake of AIB in the IHKE cell line. By contrast, addition of L-aspartate did not influence the transport of AIB in NHKE cells. L-Arginine, but not L-lysine decreased the influx in both cell lines. We conclude that the IHKE cell line has retained the capability to accumulate AIB by transport protein(s) similar to those present for neutral alpha-amino acids in NHKE cells.

Aminoisobutyric Acids↗
PubMed1983

Perturbation of alpha-aminoisobutyric acid transport in human placental membranes: direct effects by HgCl2, CH3HgCl, and CdCl2.

Mercuric chloride, methylmercuric chloride, and cadmium chloride directly affect the human placental syncytiotrophoblast microvillous membrane. These heavy metals alter the facilitated diffusion of alpha-aminoisobutyric acid (AIB) into vesicles of this membrane in microM concentrations. Mercuric chloride abolishes temporal kinetics of AIB transport, inducing an initial increase in AIB transport (27% at 100 microM) but subsequently lowering equilibrium values when compared to equilibrium time points in control. Methylmercuric chloride and cadmium chloride inhibited the initial rate of AIB transport (40% and 21%, respectively, at 200 microM), but did not affect the equilibrium value of AIB transported when compared to equilibrium levels in control. These effects were concentration dependent. Methylmercuric chloride was more potent in inhibiting AIB transport than cadmium chloride. Methylmercuric chloride and cadmium chloride effects on AIB transport were observed with minimal preincubation with placental vesicles. However, preincubation was necessary for mercuric chloride-induced perturbation of AIB transport. Cysteine protects against mercuric chloride- and methylmercuric chloride-induced effects on AIB transport but did not reverse these perturbations. Mercury- and cadmium-induced placental membrane toxicity result from interactions of these heavy metals with the placental plasma membranes.

Aminoisobutyric Acids↗
PubMed1984

Selective fetal malnutrition: the effect of nicotine, ethanol, and acetaldehyde upon in vitro uptake of alpha-aminoisobutyric acid by human term placental villous slices.

Intrauterine growth retardation (IUGR) is often associated with either tobacco smoking or ethanol abuse during pregnancy, and the two habits usually coexist. We tested the hypothesis that nicotine is placentotoxic, thereby contributing to tobacco-associated IUGR. In vitro uptake of alpha-aminoisobutyric acid (AIB) by normal human placental slices was examined in the presence of nicotine, 0.2-20 microM. Significant (p less than 0.05) reductions in AIB uptake were observed for nicotine, 2.5-20 microM, with a linear dose-response. Since ethanol, and its major metabolite, acetaldehyde, have previously been shown to impair human placental uptake of AIB, these two substances were tested for synergism with nicotine. No interaction was observed between nicotine (0.2 microM) and ethanol (1,000 mg/dl). An increased inhibition was observed for the combination of nicotine (0.2 microM) and acetaldehyde (500 microM), but two-way analysis of variance indicated that the effects are additive, rather than synergistic. It is concluded that nicotine inhibits term human placental transport of the actively transported, nonmetabolized amino acid, AIB. Such placentotoxicity may be a contributing factor in tobacco-associated IUGR. Abuse of ethanol concurrent with tobacco smoking by a pregnant woman may be more detrimental to placental amino acid transport than either substance alone.

Acetaldehyde↗
PubMed2004

New insights in dihydropyrimidine dehydrogenase deficiency: a pivotal role for beta-aminoisobutyric acid?

DPD (dihydropyrimidine dehydrogenase) constitutes the first step of the pyrimidine degradation pathway, in which the pyrimidine bases uracil and thymine are catabolized to beta-alanine and the R-enantiomer of beta-AIB (beta-aminoisobutyric acid) respectively. The S-enantiomer of beta-AIB is predominantly derived from the catabolism of valine. It has been suggested that an altered homoeostasis of beta-alanine underlies some of the clinical abnormalities encountered in patients with a DPD deficiency. In the present study, we demonstrated that only a slightly decreased concentration of beta-alanine was present in the urine and plasma, whereas normal levels of beta-alanine were present in the cerebrospinal fluid of patients with a DPD deficiency. Therefore the metabolism of beta-alanine-containing peptides, such as carnosine, may be an important factor involved in the homoeostasis of beta-alanine in patients with DPD deficiency. The mean concentration of beta-AIB was approx. 2-3-fold lower in cerebrospinal fluid and urine of patients with a DPD deficiency, when compared with controls. In contrast, strongly decreased levels (10-fold) of beta-AIB were present in the plasma of DPD patients. Our results demonstrate that, under pathological conditions, the catabolism of valine can result in the production of significant amounts of beta-AIB. Furthermore, the observation that the R-enantiomer of beta-AIB is abundantly present in the urine of DPD patients suggests that significant cross-over exists between the thymine and valine catabolic pathways.

Aminoisobutyric Acids↗
PubMed1981

Human placental cholinergic system: depression of the uptake of alpha-aminoisobutyric acid in isolated human placental villi by choline acetyltransferase inhibitors.

(2-Benzoylethyl)trimethylammonium chloride (BETA), bromoacetylcholine and 4-(1-naphthylvinyl)pyridine are potent inhibitors of choline acetyltransferase (ChA). In order to evaluate the role of acetylcholine in human placenta, the effects of the above ChA inhibitors on the uptake of [alpha-14C]aminoisobutyric acid (AIB) by isolated human placental villi were studied. All three inhibitors were able to inhibit AIB uptake by the tissue. The ID50 for BETA, the most potent compound, was about 6.2 x 10(-5) M. The blockade of AIB uptake closely paralleled the potency for inhibition of ChA in a series of keto-analogs of acetylcholine related to BETA. There was a positive relationship between the blockade of AIB uptake and the inhibition of ChA by BETA in situ. Hemicholinium-3 had no significant effect on AIB uptake. The ChA inhibitors did not exhibit significant effects on cell viability as determined by tissue lactic dehydrogenase. These observations indicate that the uptake of neutral amino acids by human placental villus is linked to acetylcholine synthesis.

Acetylcholine↗
PubMed1996

Blood-endothelial cell and blood-brain transport of L-proline, alpha-aminoisobutyric acid, and L-alanine.

We report the application of multiple time regression analysis with the in situ brain perfusion technique to measure the rates of passage between blood and brain for [14C] L-proline, [14C] L-alanine, and [14C] alpha-aminoisobutyric acid (AIB) and their rapidly reversible volumes following perfusion of these amino acids from 10 to 60 seconds. We also report on their mechanism of transport. Proline diffused through the blood-brain barrier with a transfer coefficient (Kin) of 0.55 +/- 0.15 x 10(-4) ml/s/g and had no reversible compartment. AIB had a low Kin of 0.68 +/- 0.14 x 10(-4) ml/s/g and a significant reversible volume of 4.34 +/- 0.51 x 10(-3) ml/g in parietal cortex. L-alanine had the highest transfer coefficient, 3.11 +/- 0.26 x 10(-4) ml/s/g, and a reversible volume of 10.03 +/- 0.93 x 10(-3) ml/g in the same cerebral region. Postwash procedures which remove any radiotracer in the vasculature and capillary depletion were performed for alanine and AIB, as they had significant reversible compartments, to test the possibility of rapid efflux from the endothelial cells. Results obtained from wash and capillary depletion procedures suggest that a rapid efflux could occur from endothelial cells after entry of alanine and AIB. Mechanisms of transport for L-alanine and AIB were investigated using amino acids (5 mM) as substrates and inhibitors of different amino acid transport systems. AIB transport was reduced by plasma and L-leucine and unchanged by sodium-free buffer, confirming its passage by the L1 system. L-alanine uptake was sodium-independent and not reduced by plasma. L-serine, L-cysteine, L-leucine and L-phenylalanine produced similar inhibition (66%) while L-alanine produced a lower inhibition (41%). L-arginine increased alanine uptake in cortex and thalamus. Adding L-serine to L-phenylalanine reduced the uptake only in cortex and hippocampus. These data suggest that L-alanine is transported by another L transport system different from the L1 system at the luminal membrane.

Alanine↗
PubMed2001

Structure and conformational behavior of biopolymers by density functional calculations employing periodic boundary conditions. I. The case of polyglycine, polyalanine, and poly-alpha-aminoisobutyric acid in vacuo.

Fully quantum mechanical calculations exploiting periodic boundary conditions (PBC) have been applied to the study of four different regular structures (alpha- and 3(10)-helix, fully extended and repeated gamma-turns) of the infinite polypeptides of glycine, alanine, and alpha-aminoisobutyric acid (Aib) in vacuo. alpha-Helix is predicted to be the most stable conformer for polyalanine and polyglycine, being stabilized over the 3(10)-helix mainly by more favorable dipole-dipole interactions. Contrary to previous suggestions, steric effects and hydrogen-bond strengths are comparable for both helix structures. 3(10)-Helix is preferred for poly-Aib, since in this case alpha-helix is strongly distorted due to unfavorable intrachain repulsions. Extended structures and repeated gamma-turns are much less stable than helix structures for all of the polypeptides examined, mainly due to the absence of favorable long-range interactions. The optimized geometries are in good agreement with the available experimental data and reveal a remarkable dependence on the nature of the residue forming the polypeptides; at the same time the electronic and structural parameters of each residue strongly depend on the secondary structure of the polypeptides.

Aminoisobutyric Acids↗
PubMed1986

Examination of the blood-to-brain transfer of alpha-aminoisobutyric acid and horseradish peroxidase: regional alterations in blood-brain barrier function following acute hypertension.

Blood-brain barrier (BBB) alterations following acute hypertension were studied in rats, employing as tracers in each animal both horseradish peroxidase (HRP) (MW 40,000) and [14C]alpha-aminoisobutyric acid ([14C]AIB) (MW 104). Eighteen animals were subjected to acute hypertension induced by the intravenous infusion of norepinephrine bitartrate (NE) (Levophed). Five animals injected with both tracers but not infused with NE served as controls. The brain of each animal was serially sectioned with adjacent sections processed either for macroautoradiography or for light microscopic visualization of HRP reaction product via histochemical reaction with tetramethylbenzidine. Quantitative blood-to-brain transfer constants for AIB were determined in each of 14 brain regions. Qualitative comparisons were also made between the AIB and HRP blood-to-brain extravasation patterns in each group. Acute hypertension increased cerebrovascular permeability to both AIB and HRP in most animals. Topographically, the sites of the most highly elevated AIB transfer corresponded with sites of HRP extravasation. Conversely, all sites of protein passage corresponded spatially to sites of elevated AIB transfer. Brain regions commonly showing increased permeability to both tracers included the cerebral cortices, corpus callosum, and thalamus. Importantly, some brain regions showed elevated AIB transfer constants where protein extravasation was absent. These regions included the caudate-putamen, hippocampus, basal forebrain, and cerebellum. These observations suggest that following acute hypertension, alterations in BBB permeability are not limited to vascular segments allowing protein extravasation.

Acute Disease↗
PubMed1983

Effects of porcine gastrin-releasing peptide on amylase release, 2-deoxyglucose uptake, and alpha-aminoisobutyric acid uptake in mouse pancreatic acini.

The effects of synthetic porcine gastrin-releasing peptide (pGRP), a recently isolated gut hormone, were studied in isolated mouse pancreatic acini. pGRP was found to exert direct effects on amylase release, 2-deoxyglucose ( [3H] 2DG) uptake, and alpha-aminoisobutyric acid (AIB) uptake. The stimulatory effect of pGRP on amylase release was significant at 100 pM, and maximal at 1 nM. Higher concentrations of pGRP exerted a smaller stimulatory effect on amylase release. pGRP also increased [3H]2DG uptake, exerting a detectable effect at 300 pM, and a maximal effect at 30 nM. In contrast to its stimulatory effect on amylase release and [3H]2DG uptake, pGRP inhibited AIB uptake. A significant inhibitory effect on AIB uptake occurred at 100 pM, and a maximal inhibitory effect occurred at 3 nM. Dose-response curves of pGRP for amylase release and AIB uptake were found to be biphasic. Bombesin was also found to stimulate amylase release with a biphasic dose-response curve in mouse acini. Both cholecystokinin (CCK) octapeptide and the cholinergic analog carbachol exerted similar effects in isolated mouse acini. However, the effects of pGRP were not inhibited by either dibutyryl cyclic guanosine 3',5'-monophosphate or atropine, whereas the effects of CCK octapeptide were inhibited by dibutyryl cyclic guanosine 3',5'-monophosphate and the effects of carbachol were inhibited by atropine. These results indicate that pGRP can mimic the biological effects of CCK and acetylcholine, but that its actions are probably mediated via a separate class of receptors in mouse acini.

Aminoisobutyric Acids↗
PubMed1988

Effect of dexamethasone on transport of alpha-aminoisobutyric acid and sucrose across the blood-brain barrier.

The effect of glucocorticoids on the blood-brain barrier (BBB) was studied in rats following a single injection or 3 days of dexamethasone administration. Tracers with a low permeability across the intact endothelium, [14C]sucrose and alpha-[3H]aminoisobutyric acid ([3H]AIB), were simultaneously injected intravenously in untreated rats or in rats treated with dexamethasone. Unidirectional blood-to-brain transfer constants (Ki) in 14 regions of the rat brain were determined. In regions of control brain, average Ki values for AIB and sucrose were approximately 0.0020 and 0.00060 ml g-1 min-1, respectively. The lowest transfer constants were found in caudate nucleus, hippocampus, white matter, and cerebellum. In dexamethasone-treated animals, Ki values for both sucrose and AIB markedly decreased by 30-50% in almost all brain regions. These results indicate that a single injection or 3 days of treatment with dexamethasone causes an apparent reduction in the normal BBB permeability, and dexamethasone may greatly interfere with drug delivery into brain. These observations may have an importance for the administration of drugs in brain disease in the presence of steroids.

Aminoisobutyric Acids↗
PubMed1985

Comparison of 68Ga-EDTA, [1-11 C]alpha-aminoisobutyric acid, and [99mTc]sodium pertechnetate in an experimental blood-brain barrier lesion.

Unilateral opening of the blood-brain barrier (BBB) in rats, induced by infusion of a hyperosmotic solution of mannitol into the left internal carotid artery, was applied to compare 68Ga-EDTA, [1-11C]alpha-aminoisobutyric acid (using the long-lived 14C-labeled analog), and [9mTc]sodium pertechnetate as agents for diagnosis of BBB disruption. Of the three agents and two time intervals studied, 68Ga-EDTA at 30 min postinjection gave the highest target-to-nontarget ratio. In addition, 68Ga-EDTA, unlike commonly used [99mTc]sodium pertechnetate, can be used in conjunction with positron emission tomography, which could make possible earlier and better assessment of BBB defects using 68Ga-EDTA.

Aminoisobutyric Acids↗
PubMed2004

Effects of zidovudine, stavudine and beta-aminoisobutyric acid on lipid homeostasis in mice: possible role in human fat wasting.

OBJECTIVE: Although mitochondrial DNA (mtDNA) depletion could play a role in nucleoside reverse transcriptase inhibitor-induced lipoatrophy, poor correlations between fat mtDNA levels and lipoatrophy suggest additional mechanism(s). Stavudine (d4T), zidovudine (AZT) and the thymine catabolite, beta-aminoisobutyric acid (BAIBA), but not zalcitabine (ddC) or didanosine (ddI), can increase fatty acid oxidation in liver mitochondria and plasma ketone bodies in mice. Since fat oxidation in non-adipose tissue can influence body adiposity, we sought to determine whether d4T, AZT and BAIBA can cause lipoatrophy in mice by this catabolic mechanism. METHODS: Lean or obese ob/ob mice were treated for 6 weeks with d4T, AZT or BAIBA, and lean mice with ddC or ddI. Body fat mass was assessed by dual energy X-ray absorptiometry, and mtDNA by Slot blot hybridization in epididymal fat. RESULTS: Whereas ddC or ddI did not change plasma beta-hydroxybutyrate and body fat mass, d4T, AZT and BAIBA increased plasma beta-hydroxybutyrate in lean mice suggesting increased hepatic fatty acid oxidation and ketogenesis. Despite unchanged food consumption, a supra-pharmacological dose of d4T tended to decrease, whilst AZT and BAIBA decreased body fat mass. Fat mtDNA and plasma triglycerides, cholesterol, glucose, insulin, leptin and adiponectin levels were unchanged. In obese mice, d4T, AZT and BAIBA did not increase plasma beta-hydroxybutyrate, and only AZT decreased body fat mass without reducing fat mtDNA. CONCLUSIONS: d4T and AZT can enhance hepatic fat oxidation and cause fat wasting, without decreasing adipose tissue mtDNA and without causing insulin resistance in mice. BAIBA, a thymine catabolite, reproduces these effects. These catabolic effects could play a role in the lipoatrophy, which can occur in AZT- or d4T-treated patients.

Aminoisobutyric Acids↗