Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Apr 21, 2008; 14(15): 2314-2322
Published online Apr 21, 2008. doi: 10.3748/wjg.14.2314
Munc18/SNARE proteins’ regulation of exocytosis in guinea pig duodenal Brunner’s gland acini
Laura I Cosen-Binker, Gerry P Morris, Stephen Vanner, Herbert Y Gaisano
Laura I Cosen-Binker, Herbert Y Gaisano, Department of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada
Gerry P Morris, Stephen Vanner, Gastrointestinal Diseases Research Unit, Queen’s University, Kingston, Ontario KL7 5G2, Canada
Author contributions: Cosen-Binker LI, Vanner S and Gaisano HY designed research; Cosen-Binker LI performed research; Morris GP contributed with the EM; Cosen-Binker LI, Vanner S and Gaisano HY wrote the paper.
Correspondence to: Herbert Y Gaisano, Department of Medicine, University of Toronto, Room 7226, Medical Sciences Building, Toronto, Ontario M5S 1A8, Canada. herbert.gaisano@utoronto.ca
Telephone: +1-416-9781526
Fax: +1-416-9788765
Received: January 5, 2008
Revised: March 11, 2008
Published online: April 21, 2008
Abstract

AIM: To examine the molecular mechanism of exocytosis in the Brunner’s gland acinar cell.

METHODS: We used a submucosal preparation of guinea pig duodenal Brunner’s gland acini to visualize the dilation of the ductal lumen in response to cholinergic stimulus. We correlated this to electron microscopy to determine the extent of exocytosis of the mucin-filled vesicles. We then examined the behavior of SNARE and interacting Munc18 proteins by confocal microscopy.

RESULTS: One and 6 &mgr;mol/L carbachol evoked a dose-dependent dilation of Brunner’s gland acini lumen, which correlated to the massive exocytosis of mucin. Munc18c and its cognate SNARE proteins Syntaxin-4 and SNAP-23 were localized to the apical plasma membrane, and upon cholinergic stimulation, Munc18c was displaced into the cytosol leaving Syntaxin-4 and SNAP-23 intact.

CONCLUSION: Physiologic cholinergic stimulation induces Munc18c displacement from the Brunner’s gland acinar apical plasma membrane, which enables apical membrane Syntaxin-4 and SNAP-23 to form a SNARE complex with mucin-filled vesicle SNARE proteins to affect exocytosis.

Keywords: Apical exocytosis, Brunner’s gland acini, Munc18c, Syntaxin-4, Carbachol