The inhibitory role of purinergic P2Y receptor on Mg2+ transport across intestinal epithelium-like Caco-2 monolayer
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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 Gq-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.
KeywordsCaco-2 monolayers Intestinal HCO3− secretion Mg2+ absorption Proton pump inhibitor P2Y2 receptor
This study was supported by research grants from Burapha University through the National Research Council of Thailand (138/2560), and the Faculty of Allied Health Sciences, Burapha University (AHS06/2560) to N. Thongon. We express our gratitude to Dr. Prasert Sobhon of the Faculty of Allied Health Sciences, Burapha University for his helpful suggestions and proofreading. We also thank Dr. Petcharat Trongtorsak of Allied Health Sciences, Burapha University for a very kind gift of forskolin, CCh, and nifedipine. We also thank Ms. Pattamaporn Ketkeaw and Mr. Chanin Nuekchob of the Faculty of Allied Health Sciences, Burapha University and Mr. Phongthon Kanjanasirirat of the Excellent Center for Drug Discovery (ECDD), Faculty of Science, Mahidol University for their excellent technical assistance.
TN designed and performed the experiments, analyzed and interpreted the results, and wrote and edited the manuscript. CS performed the experiments, analyzed the results, and wrote and edited the manuscript.
This study was funded by Burapha University through the National Research Council of Thailand (138/2560), and the Faculty of Allied Health Sciences, Burapha University (AHS06/2560) to N. Thongon.
Compliance with ethical standards
Conflict of interest
All authors declare that they have no competing interests.
This article does not contain any studies with human participants or animals performed by any of the authors.
- 29.Laohapitakworn S, Thongbunchoo J, Nakkrasae LI, Krishnamra N, Charoenphandhu N (2011) Parathyroid hormone (PTH) rapidly enhances CFTR-mediated HCO3 − secretion in intestinal epithelium-like Caco-2 monolayer: a novel ion regulatory action of PTH. Am J Physiol Cell Physiol 301(1):C137–C149CrossRefGoogle Scholar
- 30.Ekmekcioglu C, Ekmekcioglu A, Marktl W (2000) Magnesium transport from aqueous solutions across Caco-2 cells—an experimental model for intestinal bioavailability studies. Physiological considerations and recommendations. Magnes Res 13:93–102Google Scholar
- 35.Stenson WF, Easom RA, Riehl TE, Turk J (1993) Regulation of paracellular permeability in Caco-2 cell monolayers by protein kinase C. Am J Physiol 265(5 Pt 1):G955–G962Google Scholar
- 39.Yamazaki D, Funato Y, Miura J, Sato S, Toyosawa S, Furutani K, Kurachi Y, Omori Y, Furukawa T, Tsuda T, Kuwabata S, Mizukami S, Kikuchi K, Miki H (2013) Basolateral Mg2+ extrusion via CNNM4 mediates transcellular Mg2+ transport across epithelia: a mouse model. PLoS Genet 9(12):e1003983CrossRefGoogle Scholar
- 40.Hou J, Renigunta A, Konrad M, Gomes AS, Schneeberger EE, Pual DL, Waldegger S, Goodenough DA (2008) Clauin-16 and claudin-19 interact and form a cation-selective tight junction complex. J Clin Investig 118:619–628Google Scholar