Sodium and Chloride Ion‐Dependent Transport of β‐Alanine Across the Blood‐Brain Barrier

Komura, Junko; Tamai, Ikumi; Senmaru, Mizuho; Terasaki, Toshio; Sai, Yoshimichi; Tsuji, Akira

doi:10.1046/j.1471-4159.1996.67010330.x

Cited by 35 publications

(15 citation statements)

References 14 publications

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“…Transport is dependent upon Na + and Cl ¡ in the ratio 2:1:1 (Na + :Cl ¡ : -alanine) (Miyamoto et al 1990;Ramamoorthy et al 1994;Bakardjiev and Bauer 1994;Komura et al 1996). -alanine transport exhibits Michaelis-Menten kinetics with a Km in chick pectoral muscle of approximately 40 M (Bakardjiev and Bauer 1994;Kalyankar and Meister 1959;Winnick and Winnick 1959).…”

Section: Discussionmentioning

confidence: 99%

“…-alanine transport exhibits Michaelis-Menten kinetics with a Km in chick pectoral muscle of approximately 40 M (Bakardjiev and Bauer 1994;Kalyankar and Meister 1959;Winnick and Winnick 1959). No corresponding data exist for human muscle, although Km values in the same range have been reported for hepatocytes, neurons, astrocytes and synaptosomal membrane vesicles (Kanner and Bendahan 1990;Liu et al 1992;Komura et al 1996;Liu et al 1999). Concentrations of -alanine in human plasma are generally <5 M, and as a result -alanine transport will be operating at a low percentage of V max .…”

Section: Discussionmentioning

confidence: 99%

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The effect of 4 weeks β-alanine supplementation and isokinetic training on carnosine concentrations in type I and II human skeletal muscle fibres

et al. 2009

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Seven male students were supplemented with beta-alanine (beta-ALG) for 4 weeks (6.4 g day(-1)) and seven with a matching placebo (PLG). Subjects undertook 4 weeks of isokinetic training with the right leg (T) whilst the left leg was untrained (UT), serving as a control. Each training session consisted of 10 x 10 maximal 90 degrees extension and flexion contractions at 180 degrees /s using a Kin-Com isokinetic dynamometer, with 1 min rest between bouts. Muscle biopsies were taken from the vastus lateralis immediately before and at the end of the supplementation period. Following freeze drying muscle fibres were dissected and characterised by their MHC profile, as type I, IIa, IIx, or as hybrids of these. Carnosine was measured by HPLC. There was a significant increase in carnosine in both T and UT legs of the beta-ALG (9.63 +/- 3.92 mmol kg(-1) dry muscle and 6.55 +/- 2.36 mmol kg(-1) dry muscle respectively). There was a significant increase in the carnosine content of all fibre phentotypes, with no significant difference between types. There were no significant differences in the changes in muscle or in fibres between the T and UT legs. In contrast there was no significant change in the carnosine content in either the T or UT legs with placebo. The results indicate that 4 weeks training has no effect on the muscle carnosine content. Whilst an increase was seen with beta-alanine supplementation, this was not further influenced by training. These findings suggest that beta-alanine availability is the main factor regulating muscle carnosine synthesis.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The effect of 4 weeks β-alanine supplementation and isokinetic training on carnosine concentrations in type I and II human skeletal muscle fibres

et al. 2009

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“…Although in the case of small neutral amino acids it is not clear whether they act as cellular osmolytes, the Na ϩ -coupled transporters at the BBB may be involved in the regulation of Na ϩ efflux from the brain across the BBB. Together with the Na ϩ -dependent betaine/GABA transporter, GAT2/BGT-1 , and the Na ϩ -dependent taurine transporter (Komura et al, 1996) present at the BBB, these Na ϩ -coupled organic solute cotransporters also seem to be involved in the regulation of osmolality in the brain and in the maintenance of fluid balance across the BBB. GAT2/BGT-1 and TauT are also induced under hypertonic conditions (Bitoun and Tappaz, 2000).…”

Section: Discussionmentioning

confidence: 99%

ATA2 Is Predominantly Expressed as System A at the Blood-Brain Barrier and Acts as Brain-to-Blood Efflux Transport forl-Proline

et al. 2002

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Although system A is present at the blood-brain barrier (BBB), the physiological roles of system A have not been clarified. The efflux transport of the substrates of system A, such as L-proline (L-Pro), glycine (Gly), and ␣-methylaminoisobutyric acid (MeAIB), across the BBB was investigated using the in vivo Brain Efflux Index method. Over a period of 40 min, L 3 H]MeAIB uptake. In light of these observations, our results indicate that L-Pro and Gly are transported from the brain across the BBB, whereas MeAIB is retained in the brain. System A is involved in efflux transport for L-Pro at the BBB. The predominantly expressed ATA2 mRNA at the BBB may play a role in maintaining the concentration of small neutral amino acids and cerebral osmotic pressure in the brain under pathological conditions.The blood-brain barrier (BBB), which is formed by complex tight junctions of the brain capillary endothelial cells, segregates the circulating blood from interstitial fluid in the brain (Cornford, 1985). The BBB is well known to regulate not only the supply of nutrients and drugs to the brain from the circulating blood (Cornford, 1985;Pardridge et al., 1990), but also the efflux transport of compounds, such as P-glycoprotein, which transports anticancer and other drugs (Tsuji et al., 1992;Schinkel et al., 1994). Another transporter at the BBB is system A, a transporter of small neutral amino acids, which accepts L-alanine, L-proline, glycine, and ␣-methylaminoisobutyric acid (MeAIB) as substrates. It has been suggested that system A is present in the abluminal (brain) side of the BBB because MeAIB, which is a specific nonmetabolizable substrate for system A (Norman and Mann, 1986), is taken up in an Na ϩ -dependent manner from the brain side using isolated rat brain capillaries (Betz and Goldstein, 1978) and isolated abluminal membrane vesicles from bovine brain endothelial cells (Sanchez del Pino et al., 1995). Several investigations using brain-uptake methods have established that system A substrates undergo limited influx transport across the BBB (Oldendorf, 1971;Sershen and Lajtha, 1979). These investigations suggest that system A plays a role in the efflux transport of small neutral amino acids at the BBB to maintain their concentration in the brain (Betz and Goldstein, 1978). However, it does not fully explain this hypothesis, because the neutral amino acids are believed to be supplied from the circulating blood (Cornford, 1985). ReThis work was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture, Japan. It was also supported in part by the Suzuken Memorial Foundation, the Mochida Memorial Foundation for Medical and Pharmaceutical Research, the Uehara Memorial Foundation, the Novartis Foundation (Japan) for the Promotion of Science, the Nakatomi Foundation, the Japan Society

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“…Taurine is not involved in carnosine synthesis, but shares the same transporter as b-alanine for uptake into muscle (Komura et al 1996). Taurine is found in equally high concentrations as carnosine in muscle ) exhibiting the opposite distribution, being highest in type I fibres (Dunnett and Harris 1995;Harris et al 1998).…”

Section: Introductionmentioning

confidence: 99%

Carnosine, taurine and enzyme activities of human skeletal muscle fibres from elderly subjects with osteoarthritis and young moderately active subjects

et al. 2006

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Ageing is associated with a reduction in muscle carnosine (beta-alanyl-L-histidine), but there are no data on the changes specifically in type I and type II muscle fibres. Given the higher carnosine content of type II fibers, changes observed in whole muscle may be secondary to a shift in fibre composition. Carnosine, beta-alanine, histidine, taurine, and citrate synthase (CS) and glycogen phosphorylase (Phos), were measured in pools of single muscle fibres from freeze-dried muscle biopsies of vastus lateralis of nine elderly sedentary subjects (65-80 years) with osteoarthritis of the knee and undergoing total knee replacement, and nine young moderately active healthy subjects (20-35 years). Fibres were characterised as type I or II by myosin ATPase activity. Carnosine was 53.2% lower in type II fibres of older subjects resulting in an estimated 7% (and most probably still higher) decline in intracellular physico-chemical buffering capacity. Younger subjects showed higher CS activities in type I and higher Phos activities in type II fibres. These differences were less apparent in elderly subjects. Possible causes for the change in the carnosine content are reduced physical activity, reduced meat intake, or the result of progressive denervation.

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Sodium and Chloride Ion‐Dependent Transport of β‐Alanine Across the Blood‐Brain Barrier

Abstract: The characteristics of /3-alanine transport at the blood-brain barrier were studied by using primary cultured bovine brain capillary endothelial cells.

Cited by 35 publications

References 14 publications

The effect of 4 weeks β-alanine supplementation and isokinetic training on carnosine concentrations in type I and II human skeletal muscle fibres

The effect of 4 weeks β-alanine supplementation and isokinetic training on carnosine concentrations in type I and II human skeletal muscle fibres

ATA2 Is Predominantly Expressed as System A at the Blood-Brain Barrier and Acts as Brain-to-Blood Efflux Transport forl-Proline

Carnosine, taurine and enzyme activities of human skeletal muscle fibres from elderly subjects with osteoarthritis and young moderately active subjects

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