TY - JOUR
T1 - The inhibition by di(2-ethylhexyl)-phthalate of erg-mediated K + current in pituitary tumor (GH 3) cells
AU - Wu, Sheng Nan
AU - Yang, Wei Hsin
AU - Yeh, Chia Chen
AU - Huang, Hsien Ching
PY - 2012/5/1
Y1 - 2012/5/1
N2 - 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 GH 3 cells. Hyperpolarization-elicited K + currents in GH 3 cells bathed in high-K +, Ca 2+-free solution were examined to evaluate the effects of DEHP, DBEP, and DMGP on the ether-à-go-go-related-gene (erg) K + current (I K(erg)). Addition of DEHP to GH 3 cells suppressed the amplitude of I K(erg) in a concentration-dependent manner with an IC 50 value of 16.3 lM. With a two-pulse protocol, addition of DEHP shifted the activation curve of I K(erg) to a depolarized potential by approximately 10 mV with no change in the rate of I K(erg) deactivation. This compound did not have any effects on delayed rectifier K + current in GH 3 cells, while 4-aminopyridine-3-methanol (100 lM) suppressed this current significantly. DBEP (30 lM) had little or no effect on I K(erg), while DMGP (30 lM) slightly reduced it. In inside-out configuration, DEHP (30 lM) applied to the bath slightly reduced the activity of large-conductance Ca 2+-activated K + channels. DEHP (30 lM) 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 GH 3 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.
AB - 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 GH 3 cells. Hyperpolarization-elicited K + currents in GH 3 cells bathed in high-K +, Ca 2+-free solution were examined to evaluate the effects of DEHP, DBEP, and DMGP on the ether-à-go-go-related-gene (erg) K + current (I K(erg)). Addition of DEHP to GH 3 cells suppressed the amplitude of I K(erg) in a concentration-dependent manner with an IC 50 value of 16.3 lM. With a two-pulse protocol, addition of DEHP shifted the activation curve of I K(erg) to a depolarized potential by approximately 10 mV with no change in the rate of I K(erg) deactivation. This compound did not have any effects on delayed rectifier K + current in GH 3 cells, while 4-aminopyridine-3-methanol (100 lM) suppressed this current significantly. DBEP (30 lM) had little or no effect on I K(erg), while DMGP (30 lM) slightly reduced it. In inside-out configuration, DEHP (30 lM) applied to the bath slightly reduced the activity of large-conductance Ca 2+-activated K + channels. DEHP (30 lM) 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 GH 3 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.
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U2 - 10.1007/s00204-012-0805-7
DO - 10.1007/s00204-012-0805-7
M3 - Article
C2 - 22314968
AN - SCOPUS:84862893540
VL - 86
SP - 713
EP - 723
JO - Archiv fur Toxikologie
JF - Archiv fur Toxikologie
SN - 0003-9446
IS - 5
ER -