Effects of Alcohol on the Gall Bladder
Diminished inibitory action of ethanol on the contraction of gallbladder
isolated from chronically ethanol-fed Guinea pigs.
Ethanol is known to decrease the gallbladder contractility.
The purpose of this study was to clarify the mechanism of tolerance
to the inhibitory action of ethanol on the gallbladder contractility.
Male guinea pigs were fed ethanol (3%) or calorie-matched sucrose
in the drinking water for 4 weeks. Then, the gallbladder was isolated,
and its isometric tension was measured.
The contractile responses to KCl, BAY K8644, histamine, and phorbol
12,13-dibutyrate in the normal medium were not different between
the gallbladder strips from ethanol-fed and control guinea
pigs. Ethanol at 25 mmol/l in vitro did not affect the contractile
responses to KCl and BAY K8644 in the gallbladder strips
from both ethanol-fed and control guinea pigs. On the other hand,
ethanol at 25 mmol/l in vitro significantly inhibited the contractile
responses to histamine and phorbol 12,13-dibutyrate in the gallbladder
strips from the control guinea pigs, but it did not affect the contractile
response to histamine and significantly augmented that to phorbol
12,13-dibutyrate in the strips from the ethanol-fed guinea pigs.
Diphenhydramine, a selective H(1) receptor antagonist, abolished
the histamine contraction in gallbladder strips from both
control and ethanol-fed guinea pigs, while cimetidine, a selective
H(2) receptor antagonist, did not affect histamine contraction,
implying that histamine-induced contraction of guinea pig gallbladders
is mediated only by H(1) receptors. Verapamil (1 micromol/l) completely
inhibited the phorbol 12,13-dibutyrate-induced contraction of the
strips from both ethanol-fed and control guinea pigs. The histamine-induced
contraction was partly inhibited in the absence of Ca(2+) in the
medium. In the gallbladder strips from both ethanol-fed and control
guinea pigs, ethanol at 25 mmol/ in vitro did not affect the histamine-induced
contraction in the absence of extracellular Ca(2+).
Tolerance to the inhibitory action of ethanol developed selectively
on contractile responses to histamine and phorbol 12,13-dibutyrate.Chronic
ethanol administration produces tolerance to in vitro gallbladder
contractility mediated by the Ca(2+) entry through L-type Ca(2+)
channels linked with protein kinase C activation.
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