Tse, Chung

Medicine - Medicine - Gastroenterology

Anti-diarrheal mechanisms of Zn²+: Role of Zn² in intestinal CT secretion

Secretory diarrhea warrants global health research because it is a leading cause of childhood morbidity and Mortality in developing countries. While diarrhea can be treated with oral re-hydration solution (ORS), inclusion of .Zn2+ with ORS has been shown to reduce the duration of acute diarrhea. However, how Zn2+ improves diarrhea is not known. In secretory diarrhea, there is an excessive intestinal cr secretion which is stimulated by the elevation of intracellular cAMP and Ca2+ concentrations. It is also not known whether Zn2+ is effective against either or both of these two secretagogues. Forskolin/cAMP stimulated Cl- secretion in intestinal T84 cells is a sustained event. However, in the presence of Zn2+, it becomes transient and reduced in duration. We hypothesize that when Zn2+ and FSK are added simultaneously to T84 cells, they act synergistically to elevate [Ca2+]j which initially stimulates cr secretion. 2n2+ subsequently limits FSK stimulated cr secretion by blocking cAMP-stimulated K+ channel activity and generating the negative signal, Ins(3,4,5,6)P4 which is a potent inhibitor of Ca2+ activated cr channel on the apical membrane. Inhibiting cAMP-stimulated K+ channel inhibits the driving force for cr secretion and thus reduces cr secretion in response to FSK. Our model explains how Zn2+ improves diarrhea by reducing its duration and suggests that Zn2+ is therapeutically important as an anti-diarrheal compound that improves excessive cAMP¬mediated Cl- secretion (diarrhea). We believe that Zn2+ has substantial benefit in terms of inhibition of anion secretion and reduction of disease duration combined with low cost.

People

Yukari C. Manabe, MD

Associate Director of Global Health Research and Innovation

Robert Bollinger Jr., MD MPH

Director, Johns Hopkins Center for Clinical Global Health Education (CCGHE); Associate Director, Johns Hopkins Center for Global...

Joanne Katz, ScD MS,BSc

Associate Chair, Director of Academic Programs

Caitlin Kennedy, PhD MPH,BA

Co-Director, MPH concentration in Social and Behavioral Sciences in Public Health; Associate Director, Center for Qualitative...

Noreen Hynes, MD MPH

Director, Geographic Medicine Center of the Division of Infectious Diseases

Stefan Baral, MD MPH,MBA,MSc

Director, Key Populations Program
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June 2018

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