Involvement of intracellular Ca2+ dynamics in cytoprotective action by amino acids and cytotoxicity by sodium laurate, an absorption enhancer

Tomoyuki Okuda, Kenta Kadotsuji, Chie Takayama, Kiyonori Hanada, Fuyuki Mukaizawa, Ken-ichi Ogawara, Kazutaka Higaki, Toshikiro Kimura

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

In our previous studies, taurine (Tau) and L-glutamine protected intestinal epithelial cells from local toxicity caused by sodium laurate (C12), an absorption enhancer, while maintaining sufficient absorption-enhancing effect of C12, and it was suggested that one of the mechanisms behind cytoprotection by amino acids was to prevent intracellular Ca2+ concentration ([Ca 2+];) from increasing. In the present study, we focused on the elucidation of mechanisms by which C12 increases [Ca2+]i and by which amino acids suppress [Ca2+]i by utilizing Caco-2 cells. Removal of extracellular Ca2+ remarkably suppressed the increase of [Ca2+]i by C12. Compound 48/80, an inhibitor of phospholipase C, and verapamil, a Ca2+ channel inhibitor, also significantly prevented [Ca2+]i elevation. These results indicate that C12 augmented [Ca2+]i due to (a) influx of extracellular Ca2+ through Ca2+ channel, (b) release of Ca2+ from the endoplasmic reticulum. Cytoprotective action by amino acids was significantly attenuated by orthovanadate, an inhibitor of plasma membrane Ca2+-ATPase (PMCA), suggesting that amino acids activate PMCA to enhance the efflux of intracellular Ca2+. Furthermore, Tau enhanced the mitochondrial uptake of Ca2+, which could contribute to the decrease in [Ca2+]i. These results clearly show that amino acids protect intestinal epithelial cells from being damaged by modulating intracellular Ca2+ dynamics.

Original languageEnglish
Pages (from-to)2256-2265
Number of pages10
JournalJournal of Pharmaceutical Sciences
Volume95
Issue number10
DOIs
Publication statusPublished - Oct 2006

Keywords

  • Absorption enhancer
  • Amino acid
  • Caco-2 cells
  • Calcium
  • L-glutamine
  • Permeability
  • Safety
  • Sodium laurate
  • Taurine
  • Toxicity

ASJC Scopus subject areas

  • Pharmaceutical Science

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