The inhibition by di(2-ethylhexyl)-phthalate of erg-mediated K⁺ current in pituitary tumor (GH₃) cells.
DEHP (bis(2-ethylhexyl)-phthalate) known to be an endocrine-disrupting chemical is a widely used phthalate. Little information regarding the effects of phthalate esters on ion currents is available. In this study, the effects of DEHP and other phthalate esters (DBEP: di(2-butoxyethyl)-phthalate and DMGP: di(2-methylglycol)-phthalate) on ion currents were investigated in pituitary GH₃ cells. Hyperpolarization-elicited K⁺ currents in GH3 cells bathed in high-K⁺, Ca²⁺-free solution were examined to evaluate the effects of DEHP, DBEP, and DMGP on the ether-a`-go-go-related-gene (erg) K⁺ current (IK(erg)). Addition of DEHP to GH₃ cells suppressed the amplitude of IK(erg) in a concentration-dependent manner with an IC₅₀ value of 16.3 μM. With a two-pulse protocol, addition of DEHP shifted the activation curve of IK(erg) to a depolarized potential by approximately 10 mV with no change in the rate of IK(erg) deactivation. This compound did not have any effects on delayed rectifier K⁺ current in GH₃ cells, while 4-aminopyridine-3-methanol (100 μM) suppressed this current significantly. DBEP (30 μM) had little or no effect on IK(erg), while DMGP (30 μM) slightly reduced it. In inside-out configuration, DEHP (30 μM) applied to the bath slightly reduced the activity of large-conductance Ca²⁺-activated K⁺ channels. DEHP (30 μM) increased the frequency of spontaneous action potentials (APs); however, this compound at the same concentration had no effect on AP firing in KCNH2 siRNA-transfected GH₃ cells. The effects described herein can contribute to their actions on functional activity of endocrine or neuroendocrine cells if similar results are found in vivo.
Department of Physiology, National Cheng Kung University Medical College, No. 1 University Road, Tainan City 70101, Taiwan. snwu@mail.ncku.edu.tw
Sheng-Nan
SN
Wu
Wei-Hsin
WH
Yang
Chia-Chen
CC
Yeh
Hsien-Ching
HC
Huang
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D045744:Cell Line, Tumor; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors* / Q000235:genetics; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000037:antagonists & inhibitors*; D010795:Phthalic Acids / Q000494:pharmacology; D010911:Pituitary Neoplasms / Q000473:pathology; D034741:RNA, Small Interfering; D014162:Transfection
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010795:Phthalic Acids; D034741:RNA, Small Interfering; C574626:di-(2-methylglycol)phthalate; D004051:Diethylhexyl Phthalate