title: Effects of bile acids and the bile acid receptor FXR agonist on the respiratory rhythm in the in vitro brainstem medulla slice of neonatal Sprague-Dawley rats.
abstract: Intrahepatic cholestasis of pregnancy is always accompanied by adverse fetal outcomes such as malfunctions of respiration. Farnesoid X receptor (FXR) plays a critical role in the homeostasis of bile acids. Thus, we are determined to explore the effects of farnesoid X receptor (FXR) and five bile acids on respiratory rhythm generation and modulation of neonatal rats. Spontaneous periodic respiratory-related rhythmical discharge activity (RRDA) was recorded from hypoglossal nerves during the perfusion of modified Krebs solution. Group 1-6 was each given GW4064 and five bile acids of chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), cholic acid (CA) as well as ursodeoxycholic acid (UDCA) at different concentrations to identify their specific functions on respiratory rhythm modulations. Group 7 was applied to receive FXR blocker Z-guggulsterone and Z-guggulsterone with the above bile acids separately to explore the role of FXR in the respiratory rhythm modulation. Group 8 was given dimethyl sulfoxide (DMSO) as controls. Apart from UDCA, CDCA, DCA LCA and CA all exerted effects on RRDA recorded from hypoglossal nerves in a concentration-dependent manner. Respiratory cycle (RC), Inspiratory time (TI), Expiratory Time (TE) and Integral Amplitude (IA) were influenced and such effects could be reversed by Z-guggulsterone. FXR may contribute to the effects on the modulation of respiratory rhythm exerted by bile acids.
authors.affiliation: Department of Cardiology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Xianbao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Joint Surgery, Central Hospital of Shengli Oil Field, Dongying, China.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Cong
authors.affiliation: Department of Cardiology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Physiology, Southern Medical University, Guangzhou, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Zhujiang Hospital of Southern Medical University, Guangzhou, China.
authors.forename: Aihua
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Physiology, Southern Medical University, Guangzhou, China.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Yin
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000494:pharmacology*; D007555:Isoxazoles / Q000494:pharmacology*; D008526:Medulla Oblongata / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D011282:Pregnenediones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists* / Q000037:antagonists & inhibitors; D056152:Respiratory Rate / Q000187:drug effects*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D001647:Bile Acids and Salts; D007555:Isoxazoles; D011282:Pregnenediones; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C023617:pregna-4,17-diene-3,16-dione; C412815:GW 4064