title: Ethanol induces fluid hypersecretion from guinea-pig pancreatic duct cells.
abstract: 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. [Ca2+]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 [Ca2+]i that was dependent on the presence of extracellular Ca2+. Ethanol failed to augment secretin-stimulated secretion from ducts pretreated with an intracellular Ca2+ 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 Ca2+ mobilization.
authors.affiliation: Internal Medicine II, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishiguro
authors.forename: Shigeru B H
authors.initials: SB
authors.lastname: Ko
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Youxue
authors.initials: Y
authors.lastname: Wang
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Hamada
authors.forename: Nobumasa
authors.initials: N
authors.lastname: Mizuno
authors.forename: Motoji
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Hayakawa
authors.forename: Satoru
authors.initials: S
authors.lastname: Naruse
mesh_terms: D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002614:Chelating Agents / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D009924:Organ Culture Techniques; D010183:Pancreatic Ducts / Q000187:drug effects* / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism
chemical_list: D001639:Bicarbonates; D002492:Central Nervous System Depressants; D002614:Chelating Agents; D000431:Ethanol; D004533:Egtazic Acid; D000242:Cyclic AMP; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium