PURPOSE OF REVIEW: The 2009 review on small intestinal ion transport, in this series, focused on recent advances in duodenal bicarbonate secretion, the importance of scaffolding proteins and the pathophysiology of inflammation-associated diarrhea. The current review focuses on advances in ion-coupled solute transport, the dynamic role of the paracellular pathway in transepithelial-fluid transport and of elucidating the cellular basis of diarrheas associated with enteric infections. RECENT FINDINGS: In understanding the cellular pathophysiology underlying diarrheal diseases, there is increased focus on the role of altering Na absorptive mechanisms as well as the role of the paracellular pathway. This is not to minimize the role of Cl-secretory pathways, especially cystic fibrosis transmembrane conductance regulator (CFTR), which continues to have pleiotropic roles in modulating other transporters. The Na-glucose cotransporter (SGLT) was the first transporter ever to be cloned. Twenty-one years later, with another first, the crystal structure of the related Na-galactose transporter has been described and opens new avenues to understand structure-function relationships and intelligent drug design for transporters. SUMMARY: Progress continues to be made on integrating information obtained from reductionist models into more complex in-vivo animal models and where possible in human studies. Recognition of the coordinated regulation of cellular Na absorptive and Cl-secretory pathways together with the paracellular route in health and disease will help develop a more holistic picture of the multifaceted nature of small intestinal ion transport.
PURPOSE OF REVIEW: The 2009 review on small intestinal ion transport, in this series, focused on recent advances in duodenal bicarbonate secretion, the importance of scaffolding proteins and the pathophysiology of inflammation-associated diarrhea. The current review focuses on advances in ion-coupled solute transport, the dynamic role of the paracellular pathway in transepithelial-fluid transport and of elucidating the cellular basis of diarrheas associated with enteric infections. RECENT FINDINGS: In understanding the cellular pathophysiology underlying diarrheal diseases, there is increased focus on the role of altering Na absorptive mechanisms as well as the role of the paracellular pathway. This is not to minimize the role of Cl-secretory pathways, especially cystic fibrosis transmembrane conductance regulator (CFTR), which continues to have pleiotropic roles in modulating other transporters. The Na-glucose cotransporter (SGLT) was the first transporter ever to be cloned. Twenty-one years later, with another first, the crystal structure of the related Na-galactose transporter has been described and opens new avenues to understand structure-function relationships and intelligent drug design for transporters. SUMMARY: Progress continues to be made on integrating information obtained from reductionist models into more complex in-vivo animal models and where possible in human studies. Recognition of the coordinated regulation of cellular Na absorptive and Cl-secretory pathways together with the paracellular route in health and disease will help develop a more holistic picture of the multifaceted nature of small intestinal ion transport.
Authors: Onur Cil; Puay-Wah Phuan; Anne Marie Gillespie; Sujin Lee; Lukmanee Tradtrantip; Jianyi Yin; Ming Tse; Nicholas C Zachos; Ruxian Lin; Mark Donowitz; Alan S Verkman Journal: FASEB J Date: 2016-11-08 Impact factor: 5.191
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Authors: Johanna F Dekkers; Caroline L Wiegerinck; Hugo R de Jonge; Inez Bronsveld; Hettie M Janssens; Karin M de Winter-de Groot; Arianne M Brandsma; Nienke W M de Jong; Marcel J C Bijvelds; Bob J Scholte; Edward E S Nieuwenhuis; Stieneke van den Brink; Hans Clevers; Cornelis K van der Ent; Sabine Middendorp; Jeffrey M Beekman Journal: Nat Med Date: 2013-06-02 Impact factor: 53.440