Inhibition of voltage-gated cationic channels in rat embryonic hypothalamic neurones and C1300 neuroblastoma cells by triphenylethylene antioestrogens.
The effect of the non-steroidal antioestrogens tamoxifen and toremifene on voltage-gated cationic currents was examined in primary cultures of rat hypothalamic neurones and the C1300 mouse neuroblastoma cell line using the whole-cell patch clamp technique. When applied to the external bathing solution both tamoxifen and toremifene were able to inhibit TTX-sensitive sodium currents with IC50 values of 1-2 microM and delayed rectifier type potassium currents (IC50, 2-3 microM). However, only toremifene showed a significant inhibition of the I(A) current (IC50 3 microM). Inhibition of voltage-gated cationic currents was significantly impaired when tamoxifen was applied in a serum-containing solution. The steroidal antioestrogen ICI 182,780 did not inhibit any of the currents at 10 microM.
Hardy
S P
SP
Department of Pharmacy, University of Brighton, UK.
deFelipe
C
C
Valverde
M A
MA
D000818:Animals; D004965:Estrogen Antagonists / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects* / Q000196:embryology / Q000502:physiology; D015640:Ion Channel Gating; D051379:Mice; D009447:Neuroblastoma / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000502:physiology; D013629:Tamoxifen / Q000494:pharmacology*
D004965:Estrogen Antagonists; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D013629:Tamoxifen