The inhibitory role of purinergic P2Y receptor on Mg 2+ transport across intestinal epithelium-like Caco-2 monolayer

Abstract

The mechanism of proton pump inhibitors (PPIs) suppressing intestinal Mg²⁺ uptake is unknown. The present study aimed to investigate the role of purinergic P2Y receptors in the regulation of Mg²⁺ absorption in normal and omeprazole-treated intestinal epithelium-like Caco-2 monolayers. Omeprazole suppressed Mg²⁺ transport across Caco-2 monolayers. An agonist of the P2Y₂ receptor, but not the P2Y₄ or P2Y₆ receptor, suppressed Mg²⁺ transport across control and omeprazole-treated monolayers. Omeprazole enhanced P2Y₂ receptor expression in Caco-2 cells. Forskolin and P2Y₂ receptor agonist markedly enhanced apical HCO₃⁻ secretion by control and omeprazole-treated monolayers. The P2Y₂ receptor agonist suppressed Mg²⁺ transport and stimulated apical HCO₃⁻ secretion through the G_q-protein coupled-phospholipase C (PLC) dependent pathway. Antagonists of cystic fibrosis transmembrane conductance regulator (CFTR) and Na⁺-HCO₃⁻ cotransporter-1 (NBCe1) could nullify the inhibitory effect of P2Y₂ receptor agonist on Mg²⁺ transport across control and omeprazole-treated Caco-2 monolayers. Our results propose an inhibitory role of P2Y₂ on intestinal Mg²⁺ absorption.

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