Abstract
The mechanism of proton pump inhibitors (PPIs) suppressing intestinal Mg(2+) uptake is unknown. The present study aimed to investigate the role of purinergic P2Y receptors in the regulation of Mg(2+) absorption in normal and omeprazole-treated intestinal epithelium-like Caco-2 monolayers. Omeprazole suppressed Mg(2+) transport across Caco-2 monolayers. An agonist of the P2Y(2) receptor, but not the P2Y(4) or P2Y(6) receptor, suppressed Mg(2+) transport across control and omeprazole-treated monolayers. Omeprazole enhanced P2Y(2) receptor expression in Caco-2 cells. Forskolin and P2Y(2) receptor agonist markedly enhanced apical HCO(3)(-) secretion by control and omeprazole-treated monolayers. The P2Y(2) receptor agonist suppressed Mg(2+) transport and stimulated apical HCO(3)(-) secretion through the G(q)-protein coupled-phospholipase C (PLC) dependent pathway. Antagonists of cystic fibrosis transmembrane conductance regulator (CFTR) and Na(+)-HCO(3)(-) cotransporter-1 (NBCe1) could nullify the inhibitory effect of P2Y(2) receptor agonist on Mg(2+) transport across control and omeprazole-treated Caco-2 monolayers. Our results propose an inhibitory role of P2Y(2) on intestinal Mg(2+) absorption.