title: Free calcium and calmodulin levels in acinar carcinoma and normal acinar cells of rat pancreas.
abstract: Exposure of acinar carcinoma cells and normal acinar cells of rat pancreas to the muscarinic agonist drug carbamylcholine stimulated 45Ca2+ outflux from 45Ca2+-labeled cells. More rapid outflux of 45Ca2+ was detected for carcinoma cells following muscarinic stimulation than for normal cells. Direct fluorometric measurement of cytosolic Ca2+ under basal (unstimulated) conditions in quin 2-loaded cells revealed significantly lower concentration of free Ca2+ in carcinoma cells (approximately 180 nM) than in normal cells (approximately 200 nM). Stimulation with 1 mM carbamylcholine increased the cytosolic Ca2+ concentration in carcinoma and normal cells to approximately 1900 nM, after which carcinoma cells removed cytosolic Ca2+ at a faster rate to a post-stimulation plateau concentration of approximately 140 nM, in comparison to normal cells which obtained a post-stimulation plateau concentration of approximately 300 nM. Essentially identical differences between carcinoma and normal cells were detected upon stimulation with the peptidergic agonist cholecystokinin octapeptide. Finally, carcinoma cells demonstrated approximately 3 times greater calmodulin concentration than normal acinar cells. Also, the calmodulin antagonist drug W7 (N-6-(aminohexyl)-5-chloro-1-naphthalene sulfonamide) inhibited the carbamylcholine-induced release of intracellular Ca2+ in acinar carcinoma cells. These results indicate that neoplastic pancreatic acinar cells have retained mechanisms of muscarinic- and peptidergic-stimulated intracellular Ca2+ release, and implicate calmodulin as a regulatory factor in secretagogue activation of intracellular Ca2+ release. We propose that the more rapid decline of intracellular Ca2+ concentration following muscarinic or peptidergic stimulation and the increased intracellular calmodulin concentration indicate calmodulin-mediated down-regulation of free cytosolic Ca2+ in acinar carcinoma cells to levels lower than those of normal cells.
mesh_terms: D000818:Animals; D002118:Calcium / Q000032:analysis* / Q000378:metabolism; D002147:Calmodulin / Q000032:analysis* / Q000037:antagonists & inhibitors; D002277:Carcinoma / Q000032:analysis*; D003600:Cytosol / Q000032:analysis; D005470:Fluorometry; D006706:Homeostasis; D007473:Ion Channels / Q000378:metabolism; D008297:Male; D010179:Pancreas / Q000032:analysis; D010190:Pancreatic Neoplasms / Q000032:analysis*; D051381:Rats; D011916:Rats, Inbred F344; D011976:Receptors, Muscarinic / Q000378:metabolism
chemical_list: D002147:Calmodulin; D007473:Ion Channels; D011976:Receptors, Muscarinic; D002118:Calcium