Diminished Inibitory Action of Ethanol on the Contraction of Gallbladder Isolated from Chronically Ethanol-Fed Guinea Pigs

Abstract

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 H₁ receptor antagonist, abolished the histamine contraction in gallbladder strips from both control and ethanol-fed guinea pigs, while cimetidine, a selective H₂ receptor antagonist, did not affect histamine contraction, implying that histamine-induced contraction of guinea pig gallbladders is mediated only by H₁ receptors. Verapamil (1 µmol/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 Ca²⁺ 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 Ca²⁺. 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 Ca²⁺ entry through L-type Ca²⁺ channels linked with protein kinase C activation.

Laboratory Models Available to Study Alcohol‐Induced Organ Damage and Immune Variations: Choosing the Appropriate Model

“…Variation A of the model is used in association with a Second Hit to explore the mechanisms by which chronic alcohol abuse induces metabolic (Kudo et al, 2009;Macho et al, 2003;Seiva et al, 2009), morphological (Evrard et al, 2006;Andersson et al, 1995;Sarphie et al, 1996), immunological, and functional (Abdallah et al, 1988;Blank et al, 1991;Cook et al, 2004;Edsen-Moore et al, 2008;Meyerholz et al, 2008;Song et al, 2002;Zhu et al, 2004) changes in organs and cells and increases susceptibility to infections Masui et al, 2002). The model has also been used to study effects of (uterine) chronic alcohol abuse on fetal lung development (Gauthier et al, 2005), on bone mineral content (Broulik et al, 2009), and in the exercebation of liver damage induced by other hepatotic agents (Nadkarni and D 'Souza, 1988;Nadkarni et al, 1983).…”

Inhibitory Effect of L-Type Voltage-Dependent Calcium Channel Blocker on Response of Urinary Bladder with Acute Ethanol Intoxication

“…As ethanol has inhibitory actions on L-type VDCCs in various smooth muscles [2,10,11], it is possible that ethanol has a suppressive effect on L-type VDCCs on detrusor smooth muscles. Hereto, this is the first study to identify the depressive effect of L-type VDCC blockers in association with acute ethanol intoxication on urinary bladder contractility.…”

“…Ethanol suppresses the calcium channels on the smooth muscle membrane specifically by inhibiting the influx of calcium through L-type Ca 2+ channels and receptor-operated calcium channels and thereby displays inhibitory actions on the contraction of a variety of smooth muscles [2,3] . Ethanol suppresses L-type VDCCs in various organs [10,11] .…”

“…Ethanol is known to display inhibitory actions on the contraction of a variety of smooth muscles by disturbing the transplasmalemmal Ca 2+ entry through L-type Ca 2+ channels [2] . Ethanol suppresses the calcium channels on the smooth muscle membrane specifically by inhibiting the influx of calcium through L-type Ca 2+ channels and receptor-operated calcium channels and thereby displays inhibitory actions on the contraction of a variety of smooth muscles [2,3] . Therefore, it is possible that ethanol might have a depressive effect on the detrusor muscle via L-type Ca 2+ channels.…”

The Effect of Moderate Alcohol Intake on Gallblader Motility: A Milk Ultrasonographic Study

“…However in vivo it is unlikely that ethanol consumption would affect gallbladder motility owing to the tolerance produced towards the acute inhibitory action of ethanol. In another study, chronic ethanol administration to guinea pigs produced tolerance to in vitro gallbladder contractility mediated by the Ca2+ entry through L-type Ca2+ channels linked with protein kinase C activation [7]. Chronic alcohol consumption was reported that has no irreversible effects on clinical relevance of postprandial gastrobiliary motility, in contrast to the well documented reversible effects of acute alcohol consumption on gastric motility [8].…”