Stimulation of mucosal secretion by lubiprostone (SPI-0211) in guinea pig small intestine and colon

Actions of lubiprostone, a selective type-2 chloride channel activator, on mucosal secretion were investigated in guinea pig small intestine and colon. Flat-sheet preparations were mounted in Ussing flux chambers for recording short-circuit current (Isc) as a marker for electrogenic chloride secreti...

Full description

Saved in:
Bibliographic Details
Published in:American journal of physiology: Gastrointestinal and liver physiology 2009-04, Vol.296 (4), p.G823-G832
Main Authors: Fei, Guijun, Wang, Yu-Zhong, Liu, Sumei, Hu, Hong-Zhen, Wang, Guo-Du, Qu, Mei-Hua, Wang, Xi-Yu, Xia, Yun, Sun, Xiaohong, Bohn, Laura M, Cooke, Helen J, Wood, Jackie D
Format: Article
Language:English
Subjects:
Alprostadil - administration & dosage
Alprostadil - analogs & derivatives
Alprostadil - pharmacology
Animals
Biochemistry
Biological Transport - drug effects
Cathartics - pharmacology
Chlorides - metabolism
Colon
Colon - drug effects
Colon - metabolism
Dose-Response Relationship, Drug
Guinea Pigs
Histamine - metabolism
Intestinal Mucosa - drug effects
Intestinal Mucosa - metabolism
Intestine, Small - drug effects
Intestine, Small - metabolism
Lubiprostone
Mammals
Membranes
Mucosal Biology
Neurons
Neurons - physiology
Prostaglandins - metabolism
Small intestine
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Actions of lubiprostone, a selective type-2 chloride channel activator, on mucosal secretion were investigated in guinea pig small intestine and colon. Flat-sheet preparations were mounted in Ussing flux chambers for recording short-circuit current (Isc) as a marker for electrogenic chloride secretion. Lubiprostone, applied to the small intestinal mucosa in eight concentrations ranging from 1-3000 nM, evoked increases in Isc in a concentration-dependent manner with an EC50 of 42.5 nM. Lubiprostone applied to the mucosa of the colon in eight concentrations ranging from 1-3000 nM evoked increases in Isc in a concentration-dependent manner with an EC50 of 31.7 nM. Blockade of enteric nerves by tetrodotoxin did not influence stimulation of Isc by lubiprostone. Antagonists acting at prostaglandin (PG)E2, EP1-3, or EP4 receptors did not suppress stimulation of Isc by lubiprostone but suppressed or abolished PGE2-evoked responses. Substitution of gluconate for chloride abolished all responses to lubiprostone. The selective CFTR channel blocker, CFTR(inh)-172, did not suppress lubiprostone-evoked Isc. The broadly acting blocker, glibenclamide, suppressed (P
ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.90447.2008