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Nonylphenol affects myocardial contractility and L-type Ca2+ channel currents in a non-monotonic manner via G protein-coupled receptor 30
- Source :
- Toxicology. 334:122-129
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
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.
- Subjects :
- MAPK/ERK pathway
medicine.medical_specialty
Calcium Channels, L-Type
Guinea Pigs
Toxicology
Membrane Potentials
Receptors, G-Protein-Coupled
Rats, Sprague-Dawley
Contractility
chemistry.chemical_compound
Phenols
Internal medicine
medicine
Animals
Myocytes, Cardiac
Calcium Signaling
Ion channel
G protein-coupled receptor
Dose-Response Relationship, Drug
Chemistry
Estrogens
Myocardial Contraction
Nonylphenol
Perfusion
Kinetics
Xenoestrogen
Endocrinology
Mechanism of action
Biophysics
Female
medicine.symptom
GPER
Signal Transduction
Subjects
Details
- ISSN :
- 0300483X
- Volume :
- 334
- Database :
- OpenAIRE
- Journal :
- Toxicology
- Accession number :
- edsair.doi.dedup.....cecedabac8bd488e09f7d6c5d4caf479