title: Nonylphenol affects myocardial contractility and L-type Ca(2+) channel currents in a non-monotonic manner via G protein-coupled receptor 30.
abstract: Nonylphenol (NP) is one of the widely spread xenoestrogens (XEs) and is used in the production of industrial and consumer surfactants. In the present study, we examined the acute effects of NP on myocardial contractility to determine its rapid-response cardiac effects in the isolated heart. We also investigated the mechanism of action of NP by determining its effects on the L-type Ca(2+) channel (LTCC) currents (ICa-L) in ventricular myocytes. Lower concentrations (10(-12)-10(-10)M) of NP increased cardiac contractility while higher concentrations (10(-8)-10(-6)M) exhibited opposite effects. These apparently opposing effects suggest that NP has biphasic concentration-dependent rapid effects on cardiac contractility. These non-monotonic changes in contractility correlated with the effects of NP on ICa-L, indicating that ion channels, as rapidly responding membrane proteins, play a very important role in mediating the rapid-response effects of XEs. Further studies revealed that the G protein coupled receptor 30 (GPR30) mediates the effects of NP on LTCC at lower but not higher concentrations, implying that the differential involvement of GPR30 might be responsible for the non-monotonic effects of NP.
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, China; Department of Physiology, College of Basic Medical Sciences, China Medical University, Shenyang 110122, China.
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, China.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guo
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, China.
authors.forename: Shuice
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, China.
authors.forename: Xiangchen
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, China.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, China.
authors.forename: Xuefei
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang 110122, China. Electronic address: lyhao@mail.cmu.edu.cn.
authors.forename: Liying
authors.initials: L
authors.lastname: Hao
authors.affiliation: Laboratory of Environmental Biology and Engineering, Northeastern University, Shenyang 110004, China. Electronic address: tongzhu@mail.neu.edu.cn.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhu
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000187:drug effects* / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D006168:Guinea Pigs; D007700:Kinetics; D008564:Membrane Potentials; D009200:Myocardial Contraction / Q000187:drug effects*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010477:Perfusion; D010636:Phenols / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D020746:Calcium Channels, L-Type; D004967:Estrogens; C520305:Gper1 protein, rat; D010636:Phenols; D043562:Receptors, G-Protein-Coupled; C025256:nonylphenol
keywords: Cardiac myocytes; GPR30; L-type Ca(2+) current; Nonylphenol; Xenoestrogen