Inhibition of voltage‐gated cationic channels in rat embryonic hypothalamic neurones and C1300 neuroblastoma cells by triphenylethylene antioestrogens

FEBS Letters

deFelipe, C.³  Valverde, M.A.¹  Hardy, S.P.² 

[1] Neuroscience Research Centre, Department of Physiology, Kings College, The Strand, London WC2R 2LS, UK;Department of Pharmacy, University of Brighton, Lewes Road, Brighton BN2 4AT, UK;Instituto de Neurociencia, Universidad Miguel Hernandez, Campus de San Juan, 03550 Alicante, Spain

关键词: Hypothalamus;    Tamoxifen;    Toremifene;    ICI 182;    780;    Potassium current;    Sodium current;    4-AP;    4-aminopyridine;    DR;    delayed rectifier;    EGTA;    ethylene glycol-bis-(β-aminoethyl ether) N;    N;    N′;    N′-tetraacetic acid;    HEPES;    N-[2-hydroxyethyl] piperazine-N′-[2-ethanesulphonic acid];    MEM;    minimal essential medium;    TEA;    tetraethylammonium;   

DOI  :  10.1016/S0014-5793(98)00974-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 μM and delayed rectifier type potassium currents (IC₅₀, 2–3 μM). However, only toremifene showed a significant inhibition of the I_A current (IC₅₀ 3 μM). 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 μM.

【 授权许可】

Unknown