Transcript From Barrett KE: Ganong`s Review of Medical Physiology. Mc

ACTION OF BILE ACID ON
GALLBLADDER MUSCLE
膽汁酸於膽囊肌肉之作用
Division of Gastroenterology and Hepatology, Department of
Internal Medicine, E-Da Hospital
School of Chinese Medicine for Post-Baccalaureate, I-Shou
University
Shih-Che Huang 黃士哲
2010.10.6
INTRODUCTION
Bile acids

Solubilization of dietary lipids and
promotion of their absorption
From Barrett KE: Ganong’s Review of Medical Physiology. Mc-Graw-Hill, 2010
Human bile acids:
CA, CDCA, DCA, LCA
From Barrett KE: Ganong’s Review of Medical Physiology. Mc-Graw-Hill, 2010；23：439
Bile acids biosynthetic pathways
Secondary bile acids
Trends in Pharmacological Sciences 2009;30:570-580
Enterohepatic circulation of bile acids
From Barrett KE: Ganong’s Review of Medical Physiology. Mc-Graw-Hill, 2010；23：439
Bile acids

Bile acids act as signaling molecules
 activate the bile acid receptor, a cell-surface
G protein-coupled receptor (TGR5)
○ LCA > DCA > CDCA > CA; cAMP pathway
○ energy expenditure
 activate the farnesoid-X-receptor (FXR), a
nuclear hormone receptor
○ CDCA > LCA = DCA; transcription
○ bile acid homeostasis
Bile acid receptor (TGR5) in muscle
tissue thyroid hormone T4 --->T3
Trends in Pharmacological Sciences 2009;30:570-580
Bile acid receptor (TGR5) in intestinal, liver
and immune cells
GLP-1: glucagon-like peptide-1
Trends in Pharmacological Sciences 2009;30:570-580
Bile salt TDC inhibits gallbladder
contraction
Dose-response curves of the gallbladder to CCK alone and in the
presence of bile salts
TDC: taurodeoxycholate; TUDC: tauroursodeoxycholate
GASTROENTEROLOGY 1997;112 :1699-1706
Bile salt/acid inhibit guinea pig gallbladder
smooth muscle action potential
J Physiol. 2010;588:3295-305.
In Gpbar1 knockout mice, the rhythmic
activity of gallbladder smooth muscle is
not affected by LCA
J Physiol. 2010;588:3295-305.
Bile salt receptor GPBAR1 is expressed in
mouse and guinea pig gallbladder smooth
muscle
J Physiol. 2010;588:3295-305.
AIM
 To
investigate bile acid effects in
the human and guinea pig
gallbladder muscle
METHODS

We measured relaxation of muscle
strips from the human and guinea
pig gallbladder muscle caused by
bile acids, CA, CDCA, DCA and
LCA, in vitro.
RESULTS
Bile Acid DCA Causes Relaxation of
Human Gallbladder Muscle Strip
 Bile Acids Cause Relaxation of Carbacholcontracted Guinea Pig Gallbladder
 Bile Acids Cause Relaxation of
Endothelin-contracted Guinea Pig
Gallbladder

 (Figures are presented in the meeting place.)
RESULTS-continued
Bile Acids Cause Relaxation of Carbacholcontracted Human Gallbladder
 Bile Acids Cause Relaxation of
Endothelin-contracted Human Gallbladder
 Bile Acid Caused TTX and Atropineinsensitive Relaxation of Endothelincontracted Human Gallbladder
 Reverse transcription-polymerase chain
reaction analyses of the expression of bile
acid receptor (TGR5) mRNA

 (Figures are presented in the meeting place.)
SUMMARY
In carbachol-contracted gallbladder
muscle strips, LCA, DCA, CDCA and CA
caused relaxation.
 The relative potency for bile acids to
cause relaxation were LCA > DCA >
CDCA > CA.
 These indicate the existence of G
protein-coupled bile acid receptors
mediating bile acid-induced relaxation.

DISCUSSION
cAMP
 Immunohistochemistry


Serum bile acid levels: normal, 5 mM
 Serum
bile acid levels in cholestasis:
up to 30 mM
Take home message

Bile acids activate cell-surface G-protein
bile acid receptors, TGR5, and nuclear
receptors, FXR.

Bile acids cause relaxation of human
and guinea pig gallbladder muscle
through bile acid receptors, TGR5.