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

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.