Functional and pharmacological mechanisms of nucleoside transport across the basolateral membrane of rabbit tracheal epithelial cells

Wu, Sharon; Mathias, Neil; Kim, Kwang‐Jin; Lee, Vincent H.L.

doi:10.1016/j.lfs.2005.04.066

Cited by 3 publications

(3 citation statements)

References 40 publications

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“…Analogous to previously reported delivery of small molecule nucleoside analog therapeutics via nucleoside transporter proteins found in the upper airway (Wu et al, 2005), ATB 0,+ may be targeted as a molecular drug absorption mechanism for delivery to lung parenchyma or for transport across the pulmonary barrier into the systemic circulation. Recent studies highlight the potential of ATB 0,+ mediated transport of antiviral drugs, such as acyclovir and ganciclovir, when these parent nucleoside analog cores were covalently coupled to the side chain of anionic amino acids L ‐aspartate and L ‐glutamate, converting them into neutral derivatives (Ganapathy and Ganapathy, 2005).…”

Section: Discussionmentioning

confidence: 82%

Long‐term outcome of simultaneous kissing stenting technique with sirolimus‐eluting stent for large bifurcation coronary lesions

Kim

Park

Suh

et al. 2007

Cathet Cardio Intervent

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Section: Discussionmentioning

confidence: 82%

Long‐term outcome of simultaneous kissing stenting technique with sirolimus‐eluting stent for large bifurcation coronary lesions

Kim

Park

Suh

et al. 2007

Cathet Cardio Intervent

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“…Analogous to previously reported delivery of small molecule nucleoside analog therapeutics via nucleoside transporter proteins found in the upper airway (Wu et al, 2005), ATB 0,þ may be targeted as a molecular drug absorption mechanism for delivery to lung parenchyma or for transport across the pulmonary barrier into the systemic circulation. Recent studies highlight the potential of ATB 0,þ mediated transport of antiviral drugs, such as acyclovir and ganciclovir, when these parent nucleoside analog cores were covalently coupled to the side chain of anionic amino acids L-aspartate and L-glutamate, converting them into neutral derivatives (Ganapathy and Ganapathy, 2005).…”

Section: Discussionmentioning

confidence: 93%

Functional characterization and cloning of amino acid transporter B^0,+ (ATB^0,+) in primary cultured rat pneumocytes

Uchiyama

Fujita

Gukasyan

et al. 2007

Journal Cellular Physiology

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Cationic amino acid transport in primary cultured rat pneumocytes exhibiting characteristics of alveolar epithelial type I-like cells are described. Asymmetry and activator ion dependency of (3)H-L-arginine uptake were characterized from the apical or basolateral fluid of pneumocytes grown on permeable support. Substrate specificity of transport was evaluated as a function of (3)H-L-arginine uptake inhibition in the presence of other amino acids. Transepithelial transport studies estimated (3)H-L-arginine flux in the apical-to-basolateral and basolateral-to-apical directions. Full length cDNA of rat amino acid transporter B(0,+) (rATB(0,+)) was cloned and its relative expression level studied. Results indicate that uptake of (3)H-L-arginine from apical fluid is dependent on Na(+) and Cl(-). Zwitterionic and cationic amino acids (excluding L-proline and anionic amino acids) inhibited uptake of (3)H-L-arginine from apical, but not basolateral incubation fluid. Apical-to-basolateral transepithelial flux of (3)H-L-arginine was 20x higher than basolateral-to-apical transport. Kinetic studies of (3)H-L-arginine uptake from apical fluid revealed maximal velocity (V(max)) and Michaelis-Menten constants (K(t)) of 33.32 +/- 2.12 pmol/mg protein/15 min and 0.50 +/- 0.11 mM, respectively, in a cooperative process having a coupling ratio of 1.18 +/- 0.16 with Na(+) and 1.11 +/- 0.13 with Cl(-). Expression of rATB(0,+) mRNA was identified by RT-PCR and Northern analysis. Corresponding cloned 3.2 kb rATB(0,+) cDNA sequence exhibits pronounced homology in deduced amino acid sequence to mouse (95% identity and 97% similarity) and human (89% identity and 95% similarity) ATB(0,+) homologues. We conclude that rat pneumocytes express ATB(0,+), which may partly contribute towards recovering cationic and neutral amino acids from alveolar luminal fluid.

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“…We recently obtained evidence from primary cultured rabbit tracheal epithelial cells (RTEC) that basolateral es/ei type transport exhibits a biphasic dose response to NBMPR inhibition (Wu et al 2005). In this study, we isolated full-length cDNAs encoding a constitutive equilibrative nucleoside transporter (rbENT2) and a novel C-terminal variant rbENT2A from rabbit trachea.…”

Section: Introductionmentioning

confidence: 99%

Fine tuning of rabbit equilibrative nucleoside transporter activity by an alternatively spliced variant

Ann

Kim

et al. 2005

Journal of Drug Targeting

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The full-length cDNA encoding an equilibrative nucleoside transporter (rbENT2) and its novel C-terminal variant, rbENT2A, were isolated from rabbit trachea. Rabbit ENT2 protein consists of 456 amino acid residues; rbENT2A is shorter by 41 residues. Both rbENT2 and rbENT2A transcripts are found in rabbit tissues including intestine, kidney cortex, kidney, and trachea, at varying levels of expression. When transfected in a heterologous expression system-Madin Darby canine kidney (MDCK) epithelial cell line-both rbENT2 and rbENT2A were expressed. rbENT2 had a molecular mass of 49 kDa; rbENT2A had a molecular mass of 44 kDa. Clones of both transporters yielded functional proteins that were capable of mediating uridine uptake and efflux without the needing to be coupled to a secondary ion (e.g. Na(+)). Remarkably, rbENT2A displayed a higher affinity (K(m) = 41 microM) and a lower capacity (V(max) = 0.6 nmol/mg protein/5 min) towards substrates than rbENT2 (K(m) = 272.8 microM, V(max) = 1.26 nmol/mg protein/5 min). Pharmacological profiles showed that nitro-benzyl-mercapto-purine-ribose (NBMPR) potently inhibited (3)H-uridine uptake mediated by rbENT2A, but not uptake mediated by rbENT2. The constitutive splicing, broad expression, markedly different kinetics, and distinct pharmacological characteristics of rbENT2A appear to act in conjunction with the wild type, rbENT2, to fine-tune basolateral nucleoside transport function in rabbit trachea.

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Functional and pharmacological mechanisms of nucleoside transport across the basolateral membrane of rabbit tracheal epithelial cells

Cited by 3 publications

References 40 publications

Long‐term outcome of simultaneous kissing stenting technique with sirolimus‐eluting stent for large bifurcation coronary lesions

Long‐term outcome of simultaneous kissing stenting technique with sirolimus‐eluting stent for large bifurcation coronary lesions

Functional characterization and cloning of amino acid transporter B^0,+ (ATB^0,+) in primary cultured rat pneumocytes

Fine tuning of rabbit equilibrative nucleoside transporter activity by an alternatively spliced variant

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Functional and pharmacological mechanisms of nucleoside transport across the basolateral membrane of rabbit tracheal epithelial cells

Cited by 3 publications

References 40 publications

Long‐term outcome of simultaneous kissing stenting technique with sirolimus‐eluting stent for large bifurcation coronary lesions

Long‐term outcome of simultaneous kissing stenting technique with sirolimus‐eluting stent for large bifurcation coronary lesions

Functional characterization and cloning of amino acid transporter B0,+ (ATB0,+) in primary cultured rat pneumocytes

Fine tuning of rabbit equilibrative nucleoside transporter activity by an alternatively spliced variant

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Functional characterization and cloning of amino acid transporter B^0,+ (ATB^0,+) in primary cultured rat pneumocytes