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Na+/H+ exchanger 3 inhibitor diminishes the amino-acid-enhanced transepithelial calcium transport across the rat duodenum

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Abstract

Na+/H+ exchanger (NHE)-3 is important for intestinal absorption of nutrients and minerals, including calcium. The previous investigations have shown that the intestinal calcium absorption is also dependent on luminal nutrients, but whether aliphatic amino acids and glucose, which are abundant in the luminal fluid during a meal, similarly enhance calcium transport remains elusive. Herein, we used the in vitro Ussing chamber technique to determine epithelial electrical parameters, i.e., potential difference (PD), short-circuit current (Isc), and transepithelial resistance, as well as 45Ca flux in the rat duodenum directly exposed on the mucosal side to glucose or various amino acids. We found that mucosal glucose exposure led to the enhanced calcium transport, PD, and Isc, all of which were insensitive to NHE3 inhibitor (100 nM tenapanor). In the absence of mucosal glucose, several amino acids (12 mM in the mucosal side), i.e., alanine, isoleucine, leucine, proline, and hydroxyproline, markedly increased the duodenal calcium transport. An inhibitor for NHE3 exposure on the mucosal side completely abolished proline- and leucine-enhanced calcium transport, but not transepithelial transport of both amino acids themselves. In conclusion, glucose and certain amino acids in the mucosal side were potent stimulators of the duodenal calcium absorption, but only amino-acid-enhanced calcium transport was NHE3-dependent.

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Acknowledgements

This work was supported by grants from the Thailand Research Fund (TRF)–Mahidol University through Distinguished Research Professor Grant (DPG5780004 to N. Krishnamra), the TRF–Mahidol University through the TRF Senior Research Scholar Grant (RTA5780001 to N. Charoenphandhu), the Faculty of Science, Mahidol University (to N. Charoenphandhu and J. Thongbunchoo), the Faculty of Allied Health Sciences, Burapha University and TRF through TRF Research Scholar Award (RSA5780041 to K. Wongdee), the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission (185100 to K. Wongdee), and TRF International Research Network Program (IRN59W0002).

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Authors and Affiliations

  1. Department of Physiology, Faculty of Science, Mahidol University, Rama VI Road, Bangkok, 10400, Thailand

    Nithipak Thammayon, Panan Suntornsaratoon, Nateetip Krishnamra & Narattaphol Charoenphandhu

  2. Center of Calcium and Bone Research (COCAB), Faculty of Science, Mahidol University, Bangkok, 10400, Thailand

    Nithipak Thammayon, Kannikar Wongdee, Kornkamon Lertsuwan, Panan Suntornsaratoon, Jirawan Thongbunchoo, Nateetip Krishnamra & Narattaphol Charoenphandhu

  3. Faculty of Allied Health Sciences, Burapha University, Chonburi, 20131, Thailand

    Kannikar Wongdee

  4. Department of Biochemistry, Faculty of Science, Mahidol University, Rama VI Road, Bangkok, 10400, Thailand

    Kornkamon Lertsuwan

  5. Institute of Molecular Biosciences, Mahidol University, Nakhon Pathom, 73170, Thailand

    Narattaphol Charoenphandhu

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  1. Nithipak Thammayon
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Correspondence to Narattaphol Charoenphandhu.

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Thammayon, N., Wongdee, K., Lertsuwan, K. et al. Na+/H+ exchanger 3 inhibitor diminishes the amino-acid-enhanced transepithelial calcium transport across the rat duodenum. Amino Acids 49, 725–734 (2017). https://doi.org/10.1007/s00726-016-2374-1

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