Submitted on March 2, 2009
Revised on April 20, 2009
Accepted on May 29, 2009
Galanin inhibits caerulein-stimulated pancreatic amylase secretion via cholinergic nerves and insulin
Savio George Barreto1, Charmaine M Woods1, Colin J Carati1, Ann C Schloithe1, Surendra R Jaya1, James Toouli2, and Gino Tony P Saccone1*
1 Flinders University
2 Flinders Medical Center
* To whom correspondence should be addressed. E-mail: Gino.Saccone{at}flinders.edu.au.
Pancreatic exocrine secretion is affected by galanin, but the mechanisms involved are unclear. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on basal and stimulated pancreatic amylase secretion in-vitro. The effect of galanin on basal and carbachol and caerulein-stimulated amylase secretion from isolated murine pancreatic lobules was measured. Carbachol and caerulein concentration-response relationships were established. Lobules were co-incubated with galanin (10-12M-10-7M), carbachol (10-6M) or caerulein (10-10M). Lobules were pre-incubated with atropine (10-5M), tetrodotoxin (10-5M), hexamethonium (10-5M), or diazoxide (10-7M and 10-4M) for 30mins followed by incubation with caerulein (10-10M) alone, or combined with galanin (10-12M). Amylase secretion was expressed as percent of total lobular amylase. Immunohistochemical studies used the antigen retrieval technique and antisera for galanin receptor (GALR) 1, 2 and 3. Carbachol and caerulein stimulated amylase secretion in a concentration-dependent manner with maximal responses of 2 and 1.7 fold over control evoked at 10-6M and 10-10M, respectively. Galanin (10-12M) completely inhibited caerulein-stimulated amylase secretion but had no effect on carbachol-stimulated or basal secretion. Atropine and tetrodotoxin pre-treatment abolished the caerulein-stimulated amylase secretion while hexamethonium had no significant effect. Diazoxide significantly reduced caerulein-stimulated amylase secretion by approximately 80%. Galanin did not affect caerulein-stimulated amylase secretion in the presence of hexamethonium or diazoxide. Glucose-stimulated amylase secretion was also inhibited by galanin. Immunohistochemistry revealed islet cells labeled for GALR2. These data suggest that galanin may modulate caerulein-stimulated amylase secretion by acting on cholinergic nerves and/or islet cells possibly via GALR2 to regulate insulin release
