title: Pancreatic stellate cells produce acetylcholine and may play a role in pancreatic exocrine secretion.
abstract: The pancreatic secretagogue cholecystokinin (CCK) is widely thought to stimulate enzyme secretion by acinar cells indirectly via activation of the vagus nerve. We postulate an alternative pathway for CCK-induced pancreatic secretion. We hypothesize that neurally related pancreatic stellate cells (PSCs; located in close proximity to the basolateral aspect of acinar cells) play a regulatory role in pancreatic secretion by serving as an intermediate target for CCK and secreting the neurotransmitter acetylcholine (ACh), which, in turn, stimulates acinar enzyme secretion. To determine whether PSCs (i) exhibit CCK-dependent ACh secretion and (ii) influence acinar enzyme secretion, primary cultures of human and rat PSCs were used. Immunoblotting and/or immunofluorescence was used to detect choline acetyltransferase (ACh synthesizing enzyme), vesicular ACh transporter (VAChT), synaptophysin, and CCK receptors 1 and 2. Synaptic-like vesicles in PSCs were identified by EM. ACh secretion by PSCs exposed to 20 pM CCK was measured by LC-MS/MS. Amylase secretion by acini [pretreated with and without the muscarinic receptor antagonist atropine (10 μM) and cocultured with PSCs] was measured by colorimetry. PSCs express ACh synthesizing enzyme, VAChT, synaptophysin, and CCK receptors; exhibit CCK-dependent ACh secretion; and stimulate amylase secretion by acini, which is blocked by atropine. In conclusion, PSCs express the essential elements for ACh synthesis and secretion. CCK stimulates ACh secretion by PSCs, which, in turn, induces amylase secretion by acini. Therefore, PSCs may represent a previously unrecognized intrapancreatic pathway regulating CCK-induced pancreatic exocrine secretion.
authors.affiliation: Pancreatic Research Group, South Western Sydney Clinical School and School of Medical Sciences/Pathology, University of New South Wales, Sydney 2052, Australia. p.phillips@unsw.edu.au
authors.forename: Phoebe A
authors.initials: PA
authors.lastname: Phillips
authors.forename: Lu
authors.initials: L
authors.lastname: Yang
authors.forename: Arthur
authors.initials: A
authors.lastname: Shulkes
authors.forename: Alain
authors.initials: A
authors.lastname: Vonlaufen
authors.forename: Anne
authors.initials: A
authors.lastname: Poljak
authors.forename: Sonia
authors.initials: S
authors.lastname: Bustamante
authors.forename: Alessandra
authors.initials: A
authors.lastname: Warren
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Xu
authors.forename: Michael
authors.initials: M
authors.lastname: Guilhaus
authors.forename: Romano
authors.initials: R
authors.lastname: Pirola
authors.forename: Minoti V
authors.initials: MV
authors.lastname: Apte
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Wilson
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000681:Amylases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D018920:Coculture Techniques; D022162:Cytoplasmic Vesicles / Q000378:metabolism; D006801:Humans; D046790:Pancreas, Exocrine / Q000166:cytology / Q000378:metabolism; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism
chemical_list: D011949:Receptors, Cholecystokinin; D016708:Synaptophysin; D050494:Vesicular Acetylcholine Transport Proteins; D002766:Cholecystokinin; D002795:Choline O-Acetyltransferase; D000681:Amylases; D000109:Acetylcholine