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Inhibition of a store‐operated Ca 2+ entry pathway in human endothelial cells by the isoquinoline derivative LOE 908
Author(s) -
Encabo A.,
Romanin C.,
Birke F.W.,
Kukovetz W.R.,
Groschner Klaus
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15729.x
Subject(s) - ionomycin , thapsigargin , intracellular , biophysics , chemistry , channel blocker , ionophore , membrane potential , ion transporter , membrane , biochemistry , calcium , biology , organic chemistry
1 The novel cation channel blocker, LOE 908, was tested for its effects on Ca 2+ entry and membrane currents activated by depletion of intracellular Ca 2+ stores in human endothelial cells. 2 LOE 908 inhibited store‐operated Ca 2+ entry induced by direct depletion of Ca 2+ stores with 100 nM thapsigargin or 100 nM ionomycin with an EC 50 of 2 μ m and 4 μ m , respectively. 3 LOE 908 did not affect thapsigargin‐ or ionomycin‐induced Ca 2+ release from intracellular stores up to concentrations of 3 μ m . 4 LOE 908 reversibly suppressed thapsigargin‐ as well as ionomycin‐induced whole‐cell membrane currents. 5 The LOE 908‐sensitive membrane conductance corresponded to a cation permeability of 5.5 and 6.9 fold selectivity for Ca 2+ over K + in the presence of thapsigargin and ionomycin, respectively. 6 Our results suggest that the isoquinoline, LOE 908 is a novel, potent inhibitor of the store‐operated (capacitive) Ca 2+ entry pathway in endothelial cells.