scholarly journals Therapeutic Opportunities of GPBAR1 in Cholestatic Diseases

2022 ◽  
Vol 12 ◽  
Author(s):  
Fangling Zhang ◽  
Xiaolin Xiao ◽  
Yong Li ◽  
Hefei Wu ◽  
Xinyu Deng ◽  
...  
Keyword(s):  
Bile Acid ◽  
Biliary Tree ◽  
Cholestatic Liver Disease ◽  
Liver Inflammation ◽  
Bile Acid Pool ◽  
Disease Treatment ◽  
Improved Outcomes ◽  
Simultaneous Activation ◽  
Cholestatic Diseases ◽  
G Protein Coupled

GPBAR1, a transmembrane G protein-coupled receptor for bile acids, is widely expressed in multiple tissues in humans and rodents. In recent years, GPBAR1 has been thought to play an important role in bile homeostasis, metabolism and inflammation. This review specifically focuses on the function of GPBAR1 in cholestatic liver disease and summarizes the various pathways through which GPBAR1 acts in cholestatic models. GPBAR1 mainly regulates cholestasis in a holistic system of liver-gallbladder-gut formation. In the state of cholestasis, the activation of GPBAR1 could regulate liver inflammation, induce cholangiocyte regeneration to maintain the integrity of the biliary tree, control the hydrophobicity of the bile acid pool and promote the secretion of bile HCO3−. All these functions of GPBAR1 might be clear ways to protect against cholestatic diseases and liver injury. However, the characteristic of GPBAR1-mediated proliferation increases the risk of proliferation of cholangiocarcinoma in malignant transformed cholangiocytes. This dichotomous function of GPBAR1 limits its use in cholestasis. During disease treatment, simultaneous activation of GPBAR1 and FXR receptors often results in improved outcomes, and this strategy may become a crucial direction in the development of bile acid-activated receptors in the future.

scholarly journals Melatonin MT1 and MT2 Receptors Exhibit Distinct Effects in the Modulation of Body Temperature across the Light/Dark Cycle

2019 ◽  
Vol 20 (10) ◽  
pp. 2452 ◽  
Author(s):  
Martha López-Canul ◽  
Seung Hyun Min ◽  
Luca Posa ◽  
Danilo De Gregorio ◽  
Annalida Bedini ◽  
...  
Keyword(s):  
Body Temperature ◽  
Receptor Antagonist ◽  
Partial Agonist ◽  
Receptor Subtypes ◽  
Dark Phase ◽  
Light Phase ◽  
Dark Cycle ◽  
Simultaneous Activation ◽  
Type 3 ◽  
G Protein Coupled

Melatonin (MLT) is a neurohormone that regulates many physiological functions including sleep, pain, thermoregulation, and circadian rhythms. MLT acts mainly through two G-protein-coupled receptors named MT1 and MT2, but also through an MLT type-3 receptor (MT3). However, the role of MLT receptor subtypes in thermoregulation is still unknown. We have thus investigated the effects of selective and non-selective MLT receptor agonists/antagonists on body temperature (Tb) in rats across the 12/12-h light–dark cycle. Rectal temperature was measured every 15 min from 4:00 a.m. to 9:30 a.m. and from 4:00 p.m. to 9:30 p.m., following subcutaneous injection of each compound at either 5:00 a.m. or 5:00 p.m. MLT (40 mg/kg) had no effect when injected at 5 a.m., whereas it decreased Tb during the light phase only when injected at 5:00 p.m. This effect was blocked by the selective MT2 receptor antagonist 4P-PDOT and the non-selective MT1/MT2 receptor antagonist, luzindole, but not by the α1/MT3 receptors antagonist prazosin. However, unlike MLT, neither the selective MT1 receptor partial agonist UCM871 (14 mg/kg) nor the selective MT2 partial agonist UCM924 (40 mg/kg) altered Tb during the light phase. In contrast, UCM871 injected at 5:00 p.m. increased Tb at the beginning of the dark phase, whereas UCM924 injected at 5:00 a.m. decreased Tb at the end of the dark phase. These effects were blocked by luzindole and 4P-PDOT, respectively. The MT3 receptor agonist GR135531 (10 mg/kg) did not affect Tb. These data suggest that the simultaneous activation of both MT1 and MT2 receptors is necessary to regulate Tb during the light phase, whereas in a complex but yet unknown manner, they regulate Tb differently during the dark phase. Overall, MT1 and MT2 receptors display complementary but also distinct roles in modulating circadian fluctuations of Tb.

Overexpression of sterol 12α-hydroxylase (CYP8b1): Effect on rates of cholic acid (CA) synthesis and alteration in bile acid pool composition

2001 ◽  
Vol 120 (5) ◽  
pp. A1
Author(s):  
William M. Pandak ◽  
Phillip B. Hylemon ◽  
Patricia Bohdan ◽  
Ingemar Bjorkhem ◽  
Gosta Eggertsen ◽  
...  
Keyword(s):  
Bile Acid ◽  
Cholic Acid ◽  
Bile Acid Pool ◽  
Acid Pool

Bile acid conjugation in early stage cholestatic liver disease before and during treatment with ursodeoxycholic acid

1996 ◽  
Vol 248 (2) ◽  
pp. 175-185 ◽  
Author(s):  
Mario Fracchia ◽  
Kenneth D.R. Setchell ◽  
Andrea Crosignani ◽  
Mauro Podda ◽  
Nancy O'Connell ◽  
...  
Keyword(s):  
Liver Disease ◽  
Bile Acid ◽  
Ursodeoxycholic Acid ◽  
Early Stage ◽  
Cholestatic Liver Disease

scholarly journals Recent advances in understanding bile acid homeostasis

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2029 ◽  
Author(s):  
John YL Chiang
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Farnesoid X Receptor ◽  
Recent Advances ◽  
Bile Acid Pool Size ◽  
Bile Acid Receptor ◽  
Acid Toxicity ◽  
G Protein Coupled

Bile acids are derived from cholesterol to facilitate intestinal nutrient absorption and biliary secretion of cholesterol. Recent studies have identified bile acids as signaling molecules that activate nuclear farnesoid X receptor (FXR) and membrane G protein-coupled bile acid receptor-1 (Gpbar-1, also known as TGR5) to maintain metabolic homeostasis and protect liver and other tissues and cells from bile acid toxicity. Bile acid homeostasis is regulated by a complex mechanism of feedback and feedforward regulation that is not completely understood. This review will cover recent advances in bile acid signaling and emerging concepts about the classic and alternative bile acid synthesis pathway, bile acid composition and bile acid pool size, and intestinal bile acid signaling and gut microbiome in regulation of bile acid homeostasis.

Effect of Zanchol and Chenic Acid on Bile Acid Pool Size and Gallstones in Hamsters

1982 ◽  
Vol 283 (1) ◽  
pp. 23-31 ◽  
Author(s):  
H. Cohen ◽  
G.G. Bonorris ◽  
J.W. Marks ◽  
L.J. Schoenfield
Keyword(s):  
Bile Acid ◽  
Pool Size ◽  
Bile Acid Pool ◽  
Acid Pool ◽  
Bile Acid Pool Size

scholarly journals The G protein coupled bile acid receptor TGR5 (Gpbar1) modulates endothelin-1 signaling in liver

2020 ◽  
Author(s):  
C Klindt ◽  
M Reich ◽  
B Hellweg ◽  
J Stindt ◽  
J Rahnenführer ◽  
...  
Keyword(s):  
Bile Acid ◽  
G Protein ◽  
Acid Receptor ◽  
Endothelin 1 ◽  
Bile Acid Receptor ◽  
G Protein Coupled
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