title: Acetylcholine, ATP, bombesin, and cholecystokinin stimulate 125I efflux from a human pancreatic adenocarcinoma cell line (BxPC-3).
abstract: We have studied the effects of acetylcholine (ACh), and other agents that modulate pancreatic bicarbonate secretion, on the anion permeability of a human ductal adenocarcinoma cell line (BxPC-3). Anion permeability was monitored using an 125I efflux assay. ACh (10 microM) markedly stimulated 125I efflux from BxPC-3 cells and this response was abolished by atropine (10 microM), indicating that it is mediated by muscarinic receptors. Using transport inhibitors and ionophores, we obtained data indicating that some of the ACh-induced 125I efflux results from the opening of K+ channels, which would hyperpolarise the cell and increase the electrical driving force for 125I exit. The remaining ACh-induced 125I efflux is not mediated by anion exchangers or by Na+/K+/2Cl- cotransporters, and is probably explained by activation of an anion channel in the BxPC-3 cell membrane. Ionomycin (0.5 microM) caused a small rise in 125I efflux, indicating that this process can be triggered by an increase in intracellular calcium concentration. ATP (100 microM), ADP (100 microM), bombesin (10 nM), and cholecystokinin (CCK) (10 nM) also stimulated 125I efflux, indicating that receptors for these agents are expressed on BxPC-3 cells. We speculate that bicarbonate secretion from the human pancreas could be modulated by ACh, ATP, bombesin, and CCK via a direct effect on the duct cell.
authors.affiliation: Department of Biological Sciences, Faculty of Health Sciences, University of Sydney, New South Wales, Australia.
authors.forename: J M
authors.initials: JM
authors.lastname: Lingard
authors.forename: L
authors.initials: L
authors.lastname: al-Nakkash
authors.forename: B E
authors.initials: BE
authors.lastname: Argent
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000227:Adenine Nucleotides / Q000494:pharmacology; D000230:Adenocarcinoma / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D001839:Bombesin / Q000494:pharmacology*; D002766:Cholecystokinin / Q000494:pharmacology*; D006801:Humans; D007457:Iodine Radioisotopes; D007473:Ion Channels / Q000187:drug effects; D015759:Ionomycin / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects; D014407:Tumor Cells, Cultured
chemical_list: D000227:Adenine Nucleotides; D007457:Iodine Radioisotopes; D007473:Ion Channels; D015221:Potassium Channels; D015759:Ionomycin; D000255:Adenosine Triphosphate; D002766:Cholecystokinin; D000109:Acetylcholine; D001839:Bombesin