Dual effects of n-alcohols on fluid secretion from guinea pig pancreatic ducts.
Ethanol strongly augments secretin-stimulated, but not acetylcholine (ACh)-stimulated, fluid secretion from pancreatic duct cells. To understand its mechanism of action, we examined the effect of short-chain n-alcohols on fluid secretion and intracellular Ca(2+) concentration ([Ca(2+)](i)) in guinea pig pancreatic ducts. Fluid secretion was measured by monitoring the luminal volume of isolated interlobular ducts. [Ca(2+)](i) was estimated using fura-2 microfluorometry. Methanol and ethanol at 0.3-10 mM concentrations significantly augmented fluid secretion and induced a transient elevation of [Ca(2+)](i) in secretin- or dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP)-stimulated ducts. However, they failed to affect fluid secretion and [Ca(2+)](i) in unstimulated and ACh-stimulated ducts. In contrast, propanol and butanol at 0.3-10 mM concentrations significantly reduced fluid secretion and decreased [Ca(2+)](i) in unstimulated ducts and in ducts stimulated with secretin, DBcAMP, or ACh. Both stimulatory and inhibitory effects of n-alcohols completely disappeared after their removal from the perfusate. Propanol and butanol inhibited the plateau phase, but not the initial peak, of [Ca(2+)](i) response to ACh as well as the [Ca(2+)](i) elevation induced by thapsigargin, suggesting that they inhibit Ca(2+) influx. Removal of extracellular Ca(2+) reduced [Ca(2+)](i) in duct cells and completely abolished secretin-stimulated fluid secretion. In conclusion, there is a distinct cutoff point between ethanol (C2) and propanol (C3) in their effects on fluid secretion and [Ca(2+)](i) in duct cells. Short-chain n-alcohols appear to affect pancreatic ductal fluid secretion by activating or inhibiting the plasma membrane Ca(2+) channel.
Hamada
Hiroyuki
H
Department of Internal Medicine, Nagoya University Graduate School of Medicine, 65 Tsurumaicho, Showaku, Nagoya 466-8550, Japan.
Ishiguro
Hiroshi
H
Yamamoto
Akiko
A
Shimano-Futakuchi
Sachiko
S
Ko
Shigeru B H
SB
Yoshikawa
Toshiyuki
T
Goto
Hidemi
H
Kitagawa
Motoji
M
Hayakawa
Tetsuo
T
Seo
Yoshiteru
Y
Naruse
Satoru
S
D000433:1-Propanol / Q000494:pharmacology; D000438:Alcohols / Q000494:pharmacology*; D000818:Animals; D000440:Butanols / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D000432:Methanol / Q000494:pharmacology; D010183:Pancreatic Ducts / Q000187:drug effects* / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism*; D012633:Secretin / Q000378:metabolism
D000438:Alcohols; D000440:Butanols; D012633:Secretin; D000431:Ethanol; D000433:1-Propanol; D002118:Calcium; D000432:Methanol