Gastrin-releasing peptide stimulation of amylase release from rat pancreatic lobules involves intrapancreatic neurons.
Gastrin releasing peptide (GRP) immunoreactivity has been localized to nerve fibers innervating pancreatic acini and identified in nerve cell bodies within intrapancreatic ganglia. The role of intrapancreatic neurotransmission in GRP- and neuromedin C (NmC)-stimulated amylase release was investigated using rat pancreatic lobules in vitro. Lobule responsiveness to neuronal depolarization was demonstrated by amylase release upon exposure to 55 mM potassium (207 +/- 7% of control) or veratridine (294 +/- 12%). Both GRP and NmC produced dose-dependent increases in lobular amylase release, with ED50 values of 1.1 nM and 0.13 nM, respectively. Amylase release in response to submaximal concentrations of GRP were significantly inhibited by tetrodotoxin (78 +/- 5% of control) or hexamethonium (71 +/- 5% of control). GRP-stimulated amylase release was decreased to 71 +/- 5% of control by atropine coincubation. NmC-stimulated amylase release was not affected by tetrodotoxin, hexamethonium, or atropine. GRP (10(-10) to 10(-6) M) produced dose-dependent increments in [3H]acetylcholine release from pancreatic lobules. GRP stimulates amylase release from rat pancreatic lobules by a neurally mediated mechanism in addition to direct action on acinar membrane receptors.
Flowe
K M
KM
Department of Surgery, University of Michigan, Ann Arbor.
Welling
T H
TH
Mulholland
M W
MW
D000109:Acetylcholine / Q000378:metabolism; D000681:Amylases / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001839:Bombesin / Q000494:pharmacology*; D019886:Gastrin-Releasing Peptide; D018738:Hexamethonium / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D010179:Pancreas / Q000187:drug effects* / Q000201:enzymology / Q000294:innervation; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013779:Tetrodotoxin / Q000494:pharmacology; D014701:Veratridine / Q000494:pharmacology
D010446:Peptide Fragments; D010455:Peptides; D018738:Hexamethonium; D013779:Tetrodotoxin; D011189:Potassium Chloride; D014701:Veratridine; D001285:Atropine; D019886:Gastrin-Releasing Peptide; C040794:neuromedin C; D000681:Amylases; D000109:Acetylcholine; D001839:Bombesin