Ethanol induces fluid hypersecretion from guinea-pig pancreatic duct cells

Akiko Yamamoto, Hiroshi Ishiguro, Shigeru Ko, Atsushi Suzuki, Youxue Wang, Hiroyuki Hamada, Nobumasa Mizuno, Motoji Kitagawa, Tetsuo Hayakawa, Satoru Naruse

Research output: Contribution to journalArticle

32 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)917-926
Number of pages10
JournalJournal of Physiology
Volume551
Issue number3
DOIs
Publication statusPublished - 2003 Sep 15
Externally publishedYes

Fingerprint

Pancreatic Ducts
Fluids and Secretions
Secretin
Guinea Pigs
Ethanol
Pharmacology
Cytophotometry
Fura-2
Protein Kinase Inhibitors
Cyclic AMP-Dependent Protein Kinases
Pancreatitis
Drinking
Pancreas
Buffers

ASJC Scopus subject areas

  • Physiology

Cite this

Yamamoto, A., Ishiguro, H., Ko, S., Suzuki, A., Wang, Y., Hamada, H., ... Naruse, S. (2003). Ethanol induces fluid hypersecretion from guinea-pig pancreatic duct cells. Journal of Physiology, 551(3), 917-926. https://doi.org/10.1113/jphysiol.2003.048827

Ethanol induces fluid hypersecretion from guinea-pig pancreatic duct cells. / Yamamoto, Akiko; Ishiguro, Hiroshi; Ko, Shigeru; Suzuki, Atsushi; Wang, Youxue; Hamada, Hiroyuki; Mizuno, Nobumasa; Kitagawa, Motoji; Hayakawa, Tetsuo; Naruse, Satoru.

In: Journal of Physiology, Vol. 551, No. 3, 15.09.2003, p. 917-926.

Research output: Contribution to journalArticle

Yamamoto, A, Ishiguro, H, Ko, S, Suzuki, A, Wang, Y, Hamada, H, Mizuno, N, Kitagawa, M, Hayakawa, T & Naruse, S 2003, 'Ethanol induces fluid hypersecretion from guinea-pig pancreatic duct cells', Journal of Physiology, vol. 551, no. 3, pp. 917-926. https://doi.org/10.1113/jphysiol.2003.048827
Yamamoto, Akiko ; Ishiguro, Hiroshi ; Ko, Shigeru ; Suzuki, Atsushi ; Wang, Youxue ; Hamada, Hiroyuki ; Mizuno, Nobumasa ; Kitagawa, Motoji ; Hayakawa, Tetsuo ; Naruse, Satoru. / Ethanol induces fluid hypersecretion from guinea-pig pancreatic duct cells. In: Journal of Physiology. 2003 ; Vol. 551, No. 3. pp. 917-926.
@article{519683b29dff4b12b69e03de27b836d7,
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.",
author = "Akiko Yamamoto and Hiroshi Ishiguro and Shigeru Ko and Atsushi Suzuki and Youxue Wang and Hiroyuki Hamada and Nobumasa Mizuno and Motoji Kitagawa and Tetsuo Hayakawa and Satoru Naruse",
year = "2003",
month = "9",
day = "15",
doi = "10.1113/jphysiol.2003.048827",
language = "English",
volume = "551",
pages = "917--926",
journal = "Journal of Physiology",
issn = "0022-3751",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Ethanol induces fluid hypersecretion from guinea-pig pancreatic duct cells

AU - Yamamoto, Akiko

AU - Ishiguro, Hiroshi

AU - Ko, Shigeru

AU - Suzuki, Atsushi

AU - Wang, Youxue

AU - Hamada, Hiroyuki

AU - Mizuno, Nobumasa

AU - Kitagawa, Motoji

AU - Hayakawa, Tetsuo

AU - Naruse, Satoru

PY - 2003/9/15

Y1 - 2003/9/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85007653067&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85007653067&partnerID=8YFLogxK

U2 - 10.1113/jphysiol.2003.048827

DO - 10.1113/jphysiol.2003.048827

M3 - Article

C2 - 12847207

AN - SCOPUS:12444272245

VL - 551

SP - 917

EP - 926

JO - Journal of Physiology

JF - Journal of Physiology

SN - 0022-3751

IS - 3

ER -