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Am J Physiol Gastrointest Liver Physiol 297: G333-G339, 2009. First published June 4, 2009; doi:10.1152/ajpgi.00078.2009
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HORMONES AND SIGNALING

Galanin inhibits caerulein-stimulated pancreatic amylase secretion via cholinergic nerves and insulin

Savio G. Barreto,1 Charmaine M. Woods,1 Colin J. Carati,2 Ann C. Schloithe,1 Surendra R. Jaya,1 James Toouli,1 and Gino T. P. Saccone1

Departments of 1General and Digestive Surgery and 2Anatomy and Histology, Flinders Medical Centre and Flinders University, Adelaide, South Australia, Australia

Submitted 2 March 2009 ; accepted in final form 29 May 2009

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-, carbachol-, and caerulein-stimulated amylase secretion from isolated murine pancreatic lobules was measured. Carbachol and caerulein concentration-response relationships were established. Lobules were coincubated with galanin (10–12 M to 10–7 M), carbachol (10–6 M), or caerulein (10–10 M). Lobules were preincubated with atropine (10–5 M), tetrodotoxin (10–5 M), hexamethonium (10–5 M), or diazoxide (10–7 M and 10–4 M) for 30 min followed by incubation with caerulein (10–10 M) alone or combined with galanin (10–12 M). 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 two- and 1.7-fold over control evoked at 10–6 M and 10–10 M, respectively. Galanin (10–12 M) completely inhibited caerulein-stimulated amylase secretion but had no effect on carbachol-stimulated or basal secretion. Atropine and tetrodotoxin pretreatment abolished the caerulein-stimulated amylase secretion, whereas hexamethonium had no significant effect. Diazoxide significantly reduced caerulein-stimulated amylase secretion by ~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.

pancreatic exocrine secretion; pancreatic lobules


Address for reprint requests and other correspondence: G. T. P. Saccone, Dept. of General and Digestive Surgery, Flinders Univ., Flinders Medical Ctr., Bedford Park, South Australia, Australia 5042 (e-mail: gino.saccone{at}flinders.edu.au)






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