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 cel l bodies within intrapancreatic ganglia. The role of intrapancreatic n eurotransmission in GRP- and neuromedin C (NmC)-stimulated amylase rel ease was investigated using rat pancreatic lobules in vitro. Lobule re sponsiveness to neuronal depolarization was demonstrated by amylase re lease upon exposure to 55 mM potassium (207 +/- 7% of control) or vera tridine (294 +/- 12%). Both GRP and NmC produced dose-dependent increa ses in lobular amylase release, with ED,, values of 1.1 nM and 0.13 nM , respectively. Amylase release in response to submaximal concentratio ns of GRP were significantly inhibited by tetrodotoxin (78 +/- 5% of c ontrol) or hexamethonium (71 +/- 5% of control). GRP-stimulated amylas e release was decreased to 71 +/- 5% of control by atropine coincubati on. NmC-stimulated amylase release was not affected by tetrodotoxin, h examethonium, or atropine. GRP (10-(10) to 10(-6) M) produced dose-dep endent increments in [H-3]acetylcholine release from pancreatic lobule s. GRP stimulates amylase release from rat pancreatic lobules by a neu rally mediated mechanism in addition to direct action on acinar membra ne receptors.