Na+- and Cl--coupled active transport of nitric oxide synthase inhibitors via amino acid transport system B0,+

T. Hatanaka, T. Nakanishi, W. Huang, F. H. Leibach, Puttur D Prasad, V. Ganapathy, M. E. Ganapathy

Research output: Contribution to journalArticle

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Abstract

Nitric oxide synthase (NOS) inhibitors have therapeutic potential in the management of numerous conditions in which NO overproduction plays a critical role. Identification of transport systems in the intestine that can mediate the uptake of NOS inhibitors is important to assess the oral bioavailability and therapeutic efficacy of these potential drugs. Here, we have cloned the Na+- and Cl--coupled amino acid transport system B0,+ (ATB0,+) from the mouse colon and investigated its ability to transport NOS inhibitors. When expressed in mammalian cells, ATB0,+ can transport a variety of zwitterionic and cationic amino acids in a Na+- and Cl--coupled manner. Each of the NOS inhibitors tested compete with glycine for uptake through this transport system. Furthermore, using a tritiated analog of the NOS inhibitor NG-nitro-L-arginine, we showed that Na+- and Cl--coupled transport occurs via ATB0,+. We then studied transport of a wide variety of NOS inhibitors in Xenopus laevis oocytes expressing the cloned ATB0,+ and found that ATB0,+ can transport a broad range of zwitterionic or cationic NOS inhibitors. These data represent the first identification of an ion gradient-driven transport system for NOS inhibitors in the intestinal tract.

Original languageEnglish (US)
Pages (from-to)1035-1043
Number of pages9
JournalJournal of Clinical Investigation
Volume107
Issue number8
DOIs
StatePublished - Jan 1 2001

Fingerprint

Amino Acid Transport Systems
Active Biological Transport
Nitric Oxide Synthase
Acids
Nitroarginine
Xenopus laevis
Glycine
Biological Availability
Oocytes
Intestines
Colon
Ions
Amino Acids

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Na+- and Cl--coupled active transport of nitric oxide synthase inhibitors via amino acid transport system B0,+. / Hatanaka, T.; Nakanishi, T.; Huang, W.; Leibach, F. H.; Prasad, Puttur D; Ganapathy, V.; Ganapathy, M. E.

In: Journal of Clinical Investigation, Vol. 107, No. 8, 01.01.2001, p. 1035-1043.

Research output: Contribution to journalArticle

Hatanaka, T. ; Nakanishi, T. ; Huang, W. ; Leibach, F. H. ; Prasad, Puttur D ; Ganapathy, V. ; Ganapathy, M. E. / Na+- and Cl--coupled active transport of nitric oxide synthase inhibitors via amino acid transport system B0,+. In: Journal of Clinical Investigation. 2001 ; Vol. 107, No. 8. pp. 1035-1043.
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