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.com
Volume 8
Journal of Gastrointestinal & Digestive System
GI Diseases 2018
July 11-12, 2018
July 11-12, 2018 Sydney, Australia
15
th
International Conference on
Digestive Disorders and Gastroenterology
Luminal K+ channels blocker: A superior therapeutic intervention over zinc in secretory diarrhea
Joydeep Aoun, Paromita Sarkar, Tultul Saha, Hemanta Koley and Kazi Mirajul Haque
National Institute of Cholera and Enteric Diseases, India
T
rans-epithelial secretion and absorption of fluid and electrolytes across the intestinal epithelium is necessary formaintaining
intestinal homeostasis. During secretory diarrhea this homeostasis has been altered, secretion is predominating over
the absorption from the intestine. Massive loss of fluid into the intestinal lumen is driven by the active transport of ions,
predominately Na+, K+ and Cl-. Oral Rehydration Solution (ORS) is used to replace fluid losses and promote intestinal fluid
absorption has been the primary therapy for infectious diarrheas. An effective electrogenic secretion of Cl- is only possible if
luminal potassium channels KCa3.1 (KCNN4c) is activated. Thus potassium channel has gotten attention in respect to secretory
diarrhea. Recently we have identified TRAM-34 an inhibitor of luminal potassium channel KCNN4c is very effective against
secretory diarrhea caused by Cholera Toxin (CT) or Ace of V. cholerae, heat Stable enterotoxin (STa) of Entero Toxigenic E.
coli [ETEC], NSP4 enterotoxin of rotavirus that stimulates in vivo second messenger mediated Cl- and fluid secretion. In vitro
experiments with mouse intestinal tissue in using chamber showed that luminal addition of TRAM-34 significantly abolished
cAMP-stimulated short-circuit current (Isc), a reflector of active Cl- secretion. Whereas luminal addition of zinc did not have
any effect on cAMP stimulated Cl- secretion but serosal addition of zinc causes immediate decrease of cAMP stimulated Cl-
secretion in mouse tissue as well as human colonic T84 cell monolayers. In vivo mouse ileal loops experiment together with
electrophysiological data suggests that mucosal addition of TRAM-34 dose dependently inhibit experimental diarrhea whereas
zinc shows its activity when applied from serosal side. Moreover luminal application of TRAM-34 is equally effective against
accessory cholera enterotoxin (Ace), heat-stable (STa) enterotoxin and NSP4 stimulated diarrhea. Thus a common K+ channel
is to be involved in these enterotoxins stimulated Cl- secretion, which is inhibited by TRAM-34. Moreover toxicity study was
performed in rabbit that shows TRAM-34 has minimal toxicity with the concentration ≈ 100 greater than used to block Cl-
secretion. Thus TRAM-34 seems to be very effective and useful adjunct therapy than zinc along with ORS in secretory diarrhea.
aounjoydeep@yahoo.inJoydeep Aoun
et.al., J Gastrointest Dig Syst 2018, Volume 8
DOI: 10.4172/2161-069X-C2-067