ACTION OF BILE ACID ON GALLBLADDER MUSCLE
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ACTION OF BILE ACID ON GALLBLADDER MUSCLE 膽汁 酸於膽囊肌肉之作用 PowerPoint PPT Presentation


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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.

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ACTION OF BILE ACID ON GALLBLADDER MUSCLE 膽汁 酸於膽囊肌肉之作用

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Action of bile acid on gallbladder muscle

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

INTRODUCTIONBile 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

Human bile acids:CA, CDCA, DCA, LCA

From Barrett KE:Ganong’s Review of Medical Physiology.Mc-Graw-Hill,2010;23:439


Action of bile acid on gallbladder muscle

Bile acids biosynthetic pathways

Secondary bile acids

Trends in Pharmacological Sciences 2009;30:570-580


Enterohepatic circulation of bile acids

Enterohepatic circulation of bile acids

From Barrett KE: Ganong’s Review of Medical Physiology. Mc-Graw-Hill, 2010;23:439


Bile acids

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

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

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

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

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

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

Bile salt receptor GPBAR1 is expressed in mouse and guinea pig gallbladder smooth muscle

J Physiol. 2010;588:3295-305.


Action of bile acid on gallbladder muscle

AIM

  • To investigate bile acid effects in the human and guinea pig gallbladder muscle


Methods

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

RESULTS

  • Bile Acid DCA Causes Relaxation of Human Gallbladder Muscle Strip

  • Bile Acids Cause Relaxation of Carbachol-contracted Guinea Pig Gallbladder

  • Bile Acids Cause Relaxation of Endothelin-contracted Guinea Pig Gallbladder

    • (Figures are presented in the meeting place.)


Results continued

RESULTS-continued

  • Bile Acids Cause Relaxation of Carbachol-contracted Human Gallbladder

  • Bile Acids Cause Relaxation of Endothelin-contracted Human Gallbladder

  • Bile Acid Caused TTX and Atropine-insensitive Relaxation of Endothelin-contracted 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

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

DISCUSSION

  • cAMP

  • Immunohistochemistry

  • Serum bile acid levels: normal, 5 mM

  • Serum bile acid levels in cholestasis: up to 30 mM


Take home message

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.


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