Electrogenic Na+/HCO3- co-transporter-1 is essential for the parathyroid hormone-stimulated intestinal HCO3- secretion

被引:12
作者
Charoenphandhu, Narattaphol [1 ,2 ]
Laohapitakworn, Suparerk [2 ,3 ]
Kraidith, Kamonshanok [1 ]
Nakkrasae, La-iad [2 ,4 ]
Jongwattanapisan, Prapaporn [1 ]
Tharabenjasin, Phuntila [1 ]
Krishnamra, Nateetip [1 ,2 ]
机构
[1] Mahidol Univ, Fac Sci, Dept Physiol, Bangkok 10400, Thailand
[2] Mahidol Univ, Fac Sci, Consortium Calcium & Bone Res COCAB, Bangkok 10400, Thailand
[3] Mahidol Univ, Fac Sci, Mol Med Grad Program, Bangkok 10400, Thailand
[4] Khon Kaen Univ, Fac Sci, Dept Biol, Khon Kaen, Thailand
关键词
Caco-2; monolayer; Electrogenic Na+/HCO3- co-transporter (NBCe)-1; Ileum; Parathyroid hormone (PTH); Small interfering RNA; Ussing chamber; BICARBONATE SECRETION; EPITHELIAL-CELLS; TRANSPORT; CALCIUM; CACO-2; CFTR; ABSORPTION; PATHWAYS; COTRANSPORTER; SECRETAGOGUES;
D O I
10.1016/j.bbrc.2011.05.087
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Parathyroid hormone (PTH) was recently demonstrated to enhance the HCO3- secretion through the apical anion channel, cystic fibrosis transmembrane conductance regulator (CFTR), but how the HCO3- entered the epithelial cells was not well understood, in part, due to the lack of specific inhibitors of the basolateral HCO3- transporters. Moreover, the function of the PTH-stimulated HCO3- secretion has never been investigated in vivo. Here, we designed three specific pairs of small interfering RNA sequences to simultaneously knockdown three variants of the electrogenic Na+/HCO3- co-transporter (NBCe)-1 in the intestinal epithelium-like Caco-2 monolayer. The results showed that NBCe1 mRNA levels were markedly reduced, and the PTH-induced transepithelial current and voltage changes were diminished after triple knockdown as determined by quantitative real-time PCR and Ussing chamber technique, respectively. An in vivo ligated intestinal loop study further showed that there was an increased fluid secretion, presumably driven by HCO3- transport, in the ileum, but not in jejunum or colon, of rats administered intravenously with 2 mu g/kg body weight of rat PTH 1-34. Therefore, the present results suggested that PTH stimulated intestinal HCO3- secretion, particularly in the ileum, by inducing the basolateral HCO3- uptake via NBCe1. (C) 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:775 / 779
页数:5
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