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

Abstract

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 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.

Galanin potentiates supramaximal caerulein-stimulated pancreatic amylase secretion via its action on somatostatin secretion

“…Using isolated mouse pancreatic lobules, we have previously shown that galanin had no effect on amylase secretion under basal conditions (6). In the same report, we showed that caerulein, a CCK analog, stimulated amylase secretion in a dose-dependent manner with maximal secretion at a concentration of 10 Ϫ10 M. At higher caerulein concentrations, amylase secretion was reduced.…”

“…Immunoreactivity for galanin has been localized in pancreatic nerves and also in a subset of islets (2, 5, 13). Galanin has variable effects on pancreatic exocrine secretion and pancreatic function (6,14,20,38).Using isolated mouse pancreatic lobules, we have previously shown that galanin had no effect on amylase secretion under basal conditions (6). In the same report, we showed that caerulein, a CCK analog, stimulated amylase secretion in a dose-dependent manner with maximal secretion at a concentration of 10 Ϫ10 M. At higher caerulein concentrations, amylase secretion was reduced.…”

“…Immunoreactivity for galanin has been localized in pancreatic nerves and also in a subset of islets (2, 5, 13). Galanin has variable effects on pancreatic exocrine secretion and pancreatic function (6,14,20,38).…”

Galanin

“…More recently, the effects of galanin on basal and stimulated exocrine secretion were studied by Barreto et al (8,13,15) using a pancreatic fragment / lobule preparation (9). They demonstrated that galanin inhibited caerulein-and glucose-stimulated, but not basal (10) or carbachol-stimulated amylase secretion from isolated mouse pancreatic lobules.…”

“…Barreto et al carried their findings noted using pancreatic lobules in vitro (10,13,15) to the in vivo caerulein model of acute pancreatitis in mice. In a series of experiments where they combined the non-specific receptor antagonist of galanin (galantide) with the substance P receptor (neurokinin-1 receptor) antagonist L703,606 (12), a salivary tripeptide (feG) (11) and octreotide (14), they found that galanin may be involved in the pathogenesis of acute pancreatitis by more than one mechanism (8), viz.…”