Enhancement of intestinal calcium transport by short-chain fatty acids: roles of Na<sup>+</sup>/H<sup>+</sup> exchanger 3 and transient receptor potential vanilloid subfamily 6
Issued Date
2024-02-01
Resource Type
eISSN
15221563
Scopus ID
2-s2.0-85182734039
Pubmed ID
38073487
Journal Title
American journal of physiology. Cell physiology
Volume
326
Issue
2
Start Page
C317
End Page
C330
Rights Holder(s)
SCOPUS
Bibliographic Citation
American journal of physiology. Cell physiology Vol.326 No.2 (2024) , C317-C330
Suggested Citation
Thammayon N., Wongdee K., Teerapornpuntakit J., Panmanee J., Chanpaisaeng K., Charoensetakul N., Srimongkolpithak N., Suntornsaratoon P., Charoenphandhu N. Enhancement of intestinal calcium transport by short-chain fatty acids: roles of Na<sup>+</sup>/H<sup>+</sup> exchanger 3 and transient receptor potential vanilloid subfamily 6. American journal of physiology. Cell physiology Vol.326 No.2 (2024) , C317-C330. C330. doi:10.1152/ajpcell.00330.2023 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/95928
Title
Enhancement of intestinal calcium transport by short-chain fatty acids: roles of Na<sup>+</sup>/H<sup>+</sup> exchanger 3 and transient receptor potential vanilloid subfamily 6
Corresponding Author(s)
Other Contributor(s)
Abstract
Small organic molecules in the intestinal lumen, particularly short-chain fatty acids (SCFAs) and glucose, have long been postulated to enhance calcium absorption. Here, we used 45Ca radioactive tracer to determine calcium fluxes across the rat intestine after exposure to glucose and SCFAs. Confirming previous reports, glucose was found to increase the apical-to-basolateral calcium flux in the cecum. Under apical glucose-free conditions, SCFAs (e.g., butyrate) stimulated the cecal calcium fluxes by approximately twofold, while having no effect on proximal colon. Since SCFAs could be absorbed into the circulation, we further determined whether basolateral SCFA exposure rendered some positive actions. It was found that exposure of duodenum and cecum on the basolateral side to acetate or butyrate increased calcium fluxes. Under butyrate-rich conditions, cecal calcium transport was partially diminished by Na+/H+ exchanger 3 (NHE3) inhibitor (tenapanor) and nonselective transient receptor potential vanilloid subfamily 6 (TRPV6) inhibitor (miconazole). To confirm the contribution of TRPV6 to SCFA-stimulated calcium transport, we synthesized another TRPV6 inhibitor that was demonstrated by in silico molecular docking and molecular dynamics to occlude TRPV6 pore and diminish the glucose- and butyrate-induced calcium fluxes. Therefore, besides corroborating the importance of luminal molecules in calcium absorption, our findings provided foundation for development of more effective calcium-rich nutraceuticals in combination with various absorptive enhancers, e.g., glucose and SCFAs.NEW & NOTEWORTHY Organic molecules in the intestinal lumen, e.g., glucose and short-chain fatty acids (SCFAs), the latter of which are normally produced by microfloral fermentation, can stimulate calcium absorption dependent on transient receptor potential vanilloid subfamily 6 (TRPV6) and Na+/H+ exchanger 3 (NHE3). A selective TRPV6 inhibitor synthesized and demonstrated by in silico docking and molecular dynamics to specifically bind to the pore domain of TRPV6 was used to confirm a significant contribution of this channel. Our findings corroborate physiological significance of nutrients and SCFAs in enhancing calcium absorption.
