Transport of imino acids and non-α-amino acids across the brush-border membrane of the rabbit ileum

Munck, B. G.

doi:10.1007/bf01868734

Cited by 58 publications

(36 citation statements)

References 21 publications

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“…The K 0.5 for proline (ϳ0.2 mM) for rat SIT1 is similar to the K m values reported for System IMINO (ϳ0.3 mM) (2,5). SIT1-mediated Na ϩ -dependent imino acid transport is stereoselective and Cl Ϫ -stimulated, as described for System IMINO in intestinal and renal brush-border membrane preparations and in choroid plexus (1)(2)(3)(4)(5). Rat SIT1 is a ϳ66-kDa membrane glycoprotein and is the product of the slc6a20 gene, which has a coding region of 1848 bp.…”

Section: Sit1 Is a Nasupporting

confidence: 84%

“…We demonstrate that SIT1 is specific for imino acids and N-methylated amino acids but does not efficiently recognize other ␣-amino acids such as alanine or lysine, in keeping with the substrate profile of classical System IMINO (2). The K 0.5 for proline (ϳ0.2 mM) for rat SIT1 is similar to the K m values reported for System IMINO (ϳ0.3 mM) (2,5). SIT1-mediated Na ϩ -dependent imino acid transport is stereoselective and Cl Ϫ -stimulated, as described for System IMINO in intestinal and renal brush-border membrane preparations and in choroid plexus (1)(2)(3)(4)(5).…”

Section: Sit1 Is a Nasupporting

confidence: 81%

“…3, B and C) are not directly comparable, and we have observed that K 0. 5 Na for the leak current exceeds that for proline-evoked currents (not shown). Li ϩ also stimulated the leak current (Fig.…”

Section: Sit1 Is a Membrane Glycoprotein Of The Slc6 Transportermentioning

confidence: 84%

“…The classically described System IMINO mediates the Na ϩ -dependent transport of imino acids such as proline and pipecolate in a variety of intact tissue and membrane vesicle preparations, including intestine, choroid plexus, and kidney (1)(2)(3)(4)(5). System IMINO does not accept cationic amino acids or non-␣-amino acids.…”

mentioning

confidence: 99%

“…System IMINO does not accept cationic amino acids or non-␣-amino acids. System IMINO is moderately stereospecific for L-proline and reacts with neutral amino acids at lower affinities than with their N-methylated derivatives (2,5). Some features (substrate specificity and chloride dependence) show species differences (6).…”

mentioning

confidence: 99%

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Identification of Mammalian Proline Transporter SIT1 (SLC6A20) with Characteristics of Classical System Imino

Takanaga¹,

Mackenzie²,

Suzuki

et al. 2005

Journal of Biological Chemistry

139

129

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Amino acid homeostasis depends on specific amino acid transport systems, many of which have been characterized at the molecular level. However, the classical System IMINO, defined as the Na ؉ -dependent proline transport activity that escapes inhibition by alanine, had not been identified at the molecular level. We report here the functional characteristics and tissue distribution of Sodium/Imino-acid Transporter 1 (SIT1), which exhibits the properties of classical System IMINO. SIT1, the product of the slc6a20 gene, is a member of the SLC6 Na ؉ -and Cl ؊ -dependent neurotransmitter transporter family whose function has remained unknown. When expressed in Xenopus oocytes, rat SIT1 mediated the uptake of imino acids such as proline (K 0.5 ϳ 0.2 mM) and pipecolate, as well as N-methylated amino acids (e.g. MeAIB, sarcosine). SIT1-mediated proline transport was pH-independent and insensitive to inhibition by alanine or lysine. Proline transport was Na ؉ -dependent, Cl ؊ -stimulated, and voltage-dependent. Li ؉ , but not H ؉ , could substitute for Na ؉ . Human SIT1 also functioned as a Na ؉ -dependent proline transporter. Rat SIT1 mRNA was expressed in epithelial cells of duodenum, jejunum, ileum, stomach, cecum, colon, and kidney proximal tubule S 3 segments. SIT1 mRNA was also expressed in the choroid plexus, microglia, and meninges of the brain and in the ovary. Previous reports have documented the marked urinary hyperexcretion of proline in newborn rodents and man. We found that SIT1 was dramatically up-regulated in the kidneys of 3-day-old mice, accounting for the maturation of proline reabsorption in the mouse. The human slc6a20 gene coding SIT1 is an appropriate target for investigation of hereditary forms of iminoaciduria in man.

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Section: Sit1 Is a Nasupporting

confidence: 84%

Section: Sit1 Is a Nasupporting

confidence: 81%

Section: Sit1 Is a Membrane Glycoprotein Of The Slc6 Transportermentioning

confidence: 84%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Identification of Mammalian Proline Transporter SIT1 (SLC6A20) with Characteristics of Classical System Imino

Takanaga¹,

Mackenzie²,

Suzuki

et al. 2005

Journal of Biological Chemistry

139

129

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Absorption of Drugs after Oral Administration

Granero

Polache

2010

Pharmaceutical Sciences Encyclopedia

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After oral administration, drugs must be absorbed through the gastrointestinal tract to achieve the systemic circulation and exert their pharmacological effects. The successful formulation of an optimized oral drug delivery system requires a detailed consideration and a good understanding of the intestinal absorption process, its possibilities and limitations. This article gives an overview and update on the concepts, possibilities, and limitations of drug absorption after oral administration.

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Partially competitive inhibition of intestinal baclofen absorption by beta‐alanine, a nonessential dietary aminoacid

Polache

Plá-Delfina

Merino

1991

Biopharm & Drug Disp

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In situ intestinal absorption of baclofen in the rat in the presence of beta-alanine has been investigated. Through the perfusion of 0.50 mM baclofen solutions containing variable concentrations of the aminoacid (from 5 to 100 mM), a partially competitive inhibition of baclofen absorption was characterized: absorption rate pseudoconstants of the spasmolytic drug decrease as beta-alanine concentration increases, until a limiting value is obtained (36.8 per cent of that found for baclofen alone). A computer method was developed in order to calculate parameters governing baclofen absorption in the presence of beta-aminoacid, with the following results: Vm = 11.22 mM h-1; Km = 7.42 mM; Ki = 2.45 mM; alpha = 2.78; r = 0.998. Kinetic absorption parameters for beta-alanine in the presence of 0.50 mM baclofen were also assessed: Vm = 49.88 mM h-1; Km = 12.16 mM; r = 0.998, which, as can be expected, do not significantly differ from those previously found in the absence of the spasmolytic. It is concluded that baclofen and beta-alanine compete for the same intestinal carrier system, although the values of the interaction parameters, particularly Ki, can be more or less biased due to the limitations of the procedure and/or to the existence of some other carrier system for absorption. Possible practical implications of this phenomenon are briefly discussed.

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Transport of imino acids and non-α-amino acids across the brush-border membrane of the rabbit ileum

Cited by 58 publications

References 21 publications

Identification of Mammalian Proline Transporter SIT1 (SLC6A20) with Characteristics of Classical System Imino

Identification of Mammalian Proline Transporter SIT1 (SLC6A20) with Characteristics of Classical System Imino

Absorption of Drugs after Oral Administration

Partially competitive inhibition of intestinal baclofen absorption by beta‐alanine, a nonessential dietary aminoacid

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