title: Electrogenic Na⁺/HCO₃⁻ co-transporter-1 is essential for the parathyroid hormone-stimulated intestinal HCO₃⁻ secretion.
abstract: Parathyroid hormone (PTH) was recently demonstrated to enhance the HCO(3)(-) secretion through the apical anion channel, cystic fibrosis transmembrane conductance regulator (CFTR), but how the HCO(3)(-) entered the epithelial cells was not well understood, in part, due to the lack of specific inhibitors of the basolateral HCO(3)(-) transporters. Moreover, the function of the PTH-stimulated HCO(3)(-) 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(+)/HCO(3)(-) 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 HCO(3)(-) transport, in the ileum, but not in jejunum or colon, of rats administered intravenously with 2 μg/kg body weight of rat PTH 1-34. Therefore, the present results suggested that PTH stimulated intestinal HCO(3)(-) secretion, particularly in the ileum, by inducing the basolateral HCO(3)(-) uptake via NBCe1.
authors.affiliation: Consortium for Calcium and Bone Research, Faculty of Science, Mahidol University, Bangkok, Thailand. naratt@narattsys.com
authors.forename: Narattaphol
authors.initials: N
authors.lastname: Charoenphandhu
authors.forename: Suparerk
authors.initials: S
authors.lastname: Laohapitakworn
authors.forename: Kamonshanok
authors.initials: K
authors.lastname: Kraidith
authors.forename: La-Iad
authors.initials: LI
authors.lastname: Nakkrasae
authors.forename: Prapaporn
authors.initials: P
authors.lastname: Jongwattanapisan
authors.forename: Phuntila
authors.initials: P
authors.lastname: Tharabenjasin
authors.forename: Nateetip
authors.initials: N
authors.lastname: Krishnamra
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D018938:Caco-2 Cells; D005260:Female; D055785:Gene Knockdown Techniques; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D027982:Sodium-Bicarbonate Symporters / Q000235:genetics / Q000502:physiology*; D019379:Teriparatide / Q000008:administration & dosage / Q000031:analogs & derivatives
chemical_list: D001639:Bicarbonates; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C498898:SLC4A4 protein, human; D027982:Sodium-Bicarbonate Symporters; D019379:Teriparatide; C035748:parathyroid hormone (1-34)amide