title: Bilirubin modulates acetylcholine receptors in rat superior cervical ganglionic neurons in a bidirectional manner.
abstract: Autonomic dysfunction as a partial contributing factor to cardiovascular instability in jaundiced patients is often associated with increased serum bilirubin levels. Whether increased serum bilirubin levels could directly inhibit sympathetic ganglion transmission by blocking neuronal nicotinic acetylcholine receptors (nAChRs) remains to be elucidated. Conventional patch-clamp recordings were used to study the effect of bilirubin on nAChRs currents from enzymatically dissociated rat superior cervical ganglia (SCG) neurons. The results showed that low concnetrations (0.5 and 2 μM) of bilirubin enhanced the peak ACh-evoked currents, while high concentrations (3 to 5.5 µM) of bilirubin suppressed the currents with an IC50 of 4 ± 0.5 μM. In addition, bilirubin decreased the extent of desensitization of nAChRs in a concentration-dependent manner. This inhibitory effect of bilirubin on nAChRs channel currents was non-competitive and voltage independent. Bilirubin partly improved the inhibitory effect of forskolin on ACh-induced currents without affecting the action of H-89. These data suggest that the dual effects of enhancement and suppression of bilirubin on nAChR function may be ascribed to the action mechanism of positive allosteric modulation and direct blockade. Thus, suppression of sympathetic ganglionic transmission through postganglionic nAChRs inhibition may partially contribute to the adverse cardiovascular effects in jaundiced patients.
authors.affiliation: 1] Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China [2] Department of Anesthesiology, Xinhua Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Chengmi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China.
authors.forename: Zhenmeng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China.
authors.forename: Ruirui
authors.initials: R
authors.lastname: Pan
authors.affiliation: Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Qiu
authors.affiliation: Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China.
authors.forename: Jinmin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Clinical Diagnosis, Changhai Hospital, the Second Military Medical University, Shanghai, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Shanghai First People's Hospital, Shanghai Jiaotong University, Shanghai, China.
authors.forename: Jijian
authors.initials: J
authors.lastname: Zheng
authors.affiliation: Department of Anesthesiology, Eastern Hepatobiliary Surgery Hospital, the Second Military Medical University, Shanghai, China.
authors.forename: Weifeng
authors.initials: W
authors.lastname: Yu
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000494:pharmacology*; D001663:Bilirubin / Q000494:pharmacology*; D002478:Cells, Cultured; D004594:Electrophysiology; D007473:Ion Channels / Q000187:drug effects*; D008297:Male; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000975:Antioxidants; D007473:Ion Channels; D011978:Receptors, Nicotinic; D001663:Bilirubin