Galanin potentiates supramaximal caerulein-stimulated pancreatic amylase secretion via its action on somatostatin secretion.
Galanin inhibits pancreatic amylase secretion from mouse lobules induced by physiological concentrations of caerulein via an insulin-dependent mechanism. We aimed to determine the effect and elucidate the mechanism of action of exogenous galanin on pancreatic amylase secretion induced by supramaximal concentrations of caerulein. Amylase secretion from isolated murine pancreatic lobules was measured. Lobules were coincubated with galanin (10(-12)-10(-7) M) and caerulein (10(-7) M). Lobules were preincubated with atropine (10(-5) M), tetrodotoxin (10(-5) M), diazoxide (10(-7) M), or the galanin antagonist galantide (10(-12)-10(-7) M) for 30 min followed by incubation with caerulein alone, or combined with galanin (10(-12) M). Lobules were also coincubated with combinations of galanin (10(-12) M), caerulein, octreotide (10(-12)-10(-7) M) or cyclo-(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[BZL]), a somatostatin receptor antagonist (10(-9) M). Amylase secretion was expressed as percent of total lobular amylase. Caerulein stimulated amylase secretion to 124% of control. Diazoxide pretreatment abolished the caerulein-stimulated amylase secretion, whereas atropine or tetrodotoxin caused a partial inhibition. Galanin (10(-12)-10(-7) M) potentiated caerulein-stimulated amylase secretion to 160% of control. Preincubation with a combination of atropine and diazoxide abolished the potentiating effect of galanin, indicating muscarinic receptor and insulin mediation. Preincubation with galantide abolished the galanin effect, implying galanin receptor involvement. Coincubation with caerulein, galanin, and octreotide significantly reduced the potentiating effect galanin. However, coincubation with the somatostatin receptor antagonist, alone or in combination with galanin, significantly increased caerulein-stimulated amylase secretion to a level comparable to the galanin potentiation. Taken together, these data suggest that, at supramaximal caerulein concentrations, galanin acts via its receptors to further increase caerulein-stimulated amylase secretion by inhibiting the caerulein-induced release of somatostatin.
Dept. of General and Digestive Surgery, Flinders Univ., Flinders Medical Ctr., Adelaide, South Australia, Australia.
Savio G
SG
Barreto
Colin J
CJ
Carati
Ann C
AC
Schloithe
James
J
Toouli
Gino T P
GT
Saccone
D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002108:Ceruletide / Q000494:pharmacology*; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019004:Galanin / Q000031:analogs & derivatives / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism; D051379:Mice; D018727:Muscarinic Antagonists / Q000494:pharmacology; D015282:Octreotide / Q000494:pharmacology; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D044088:Receptors, Galanin / Q000187:drug effects / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
D007328:Insulin; D018727:Muscarinic Antagonists; D044088:Receptors, Galanin; D017481:Receptors, Somatostatin; C074975:galantide; D013373:Substance P; D013779:Tetrodotoxin; D013004:Somatostatin; D001285:Atropine; C043820:cyclo(7-aminoheptanoylphenylalanyl-tryptophyl-lysyl-benzylthreonyl); D019004:Galanin; D002108:Ceruletide; D000681:Amylases; D003981:Diazoxide; D015282:Octreotide