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Ethanol induces fluid hypersecretion from guinea‐pig pancreatic duct cells
Author(s) -
Yamamoto Akiko,
Ishiguro Hiroshi,
Ko Shigeru B. H.,
Suzuki Atsushi,
Wang Youxue,
Hamada Hiroyuki,
Mizuno Nobumasa,
Kitagawa Motoji,
Hayakawa Tetsuo,
Naruse Satoru
Publication year - 2003
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.2003.00917.x
Subject(s) - peristalsis , anatomy , pacemaker potential , chemistry , medicine , syncytium , duct (anatomy) , smooth muscle , electrophysiology , biology , endocrinology , microbiology and biotechnology , biochemistry , cell
Ethanol is the leading cause of pancreatitis; however, its cellular effects are poorly understood. We examined the direct effects of ethanol in the concentration range 0.1‐30 mM, i.e. relevant to usual levels of drinking, on fluid secretion from guinea‐pig pancreatic duct cells. Fluid secretion was continuously measured by monitoring the luminal volume of interlobular duct segments isolated from the guinea‐pig pancreas. [Ca 2+ ] i was estimated by microfluorometry in duct cells loaded with fura‐2. Ethanol at 0.3‐30 mM significantly augmented fluid secretion stimulated by physiological (1 pM) or pharmacological (1 nM) concentrations of secretin. It augmented dibutyryl cAMP‐stimulated fluid secretion but failed to affect spontaneous or acethylcholine‐stimulated secretion. Ethanol at 1 mM shifted the secretin concentration‐fluid secretion response curve upwards and raised the maximal secretory response significantly by 41 %. In secretin‐stimulated ducts, 1 mM ethanol induced a transient increase in [Ca 2+ ] i that was dependent on the presence of extracellular Ca 2+ . Ethanol failed to augment secretin‐stimulated secretion from ducts pretreated with an intracellular Ca 2+ buffer (BAPTA) or a protein kinase A inhibitor (H89). In conclusion, low concentrations of ethanol directly augment pancreatic ductal fluid secretion stimulated by physiological and pharmacological concentrations of secretin, and this appears to be mediated by the activation of both the intracellular cAMP pathway and Ca 2+ mobilization.