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 journalArticle

14 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

Fingerprint

lauric acid
Cytotoxicity
Amino Acids
Calcium-Transporting ATPases
Taurine
Cell membranes
Epithelial Cells
Cell Membrane
p-Methoxy-N-methylphenethylamine
Vanadates
Cytoprotection
Caco-2 Cells
Type C Phospholipases
Verapamil
Glutamine
Endoplasmic Reticulum
Toxicity

Keywords

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

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science

Cite this

Involvement of intracellular Ca2+ dynamics in cytoprotective action by amino acids and cytotoxicity by sodium laurate, an absorption enhancer. / Okuda, Tomoyuki; Kadotsuji, Kenta; Takayama, Chie; Hanada, Kiyonori; Mukaizawa, Fuyuki; Ogawara, Ken Ichi; Higaki, Kazutaka; Kimura, Toshikiro.

In: Journal of Pharmaceutical Sciences, Vol. 95, No. 10, 10.2006, p. 2256-2265.

Research output: Contribution to journalArticle

Okuda, Tomoyuki ; Kadotsuji, Kenta ; Takayama, Chie ; Hanada, Kiyonori ; Mukaizawa, Fuyuki ; Ogawara, Ken Ichi ; Higaki, Kazutaka ; Kimura, Toshikiro. / Involvement of intracellular Ca2+ dynamics in cytoprotective action by amino acids and cytotoxicity by sodium laurate, an absorption enhancer. In: Journal of Pharmaceutical Sciences. 2006 ; Vol. 95, No. 10. pp. 2256-2265.
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AU - Hanada, Kiyonori

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