Unique properties of the capacitative Ca(2+)-entry antagonist LU 52396: its inhibitory activity depends on the activation state of the cells.
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Unique properties of the capacitative Ca(2+)-entry antagonist LU 52396: its inhibitory activity depends on the activation state of the cells. / Guse, A H; de Wit, C; Klokow, T; Schweitzer, K; Mayr, Georg W.
In: CELL CALCIUM, Vol. 22, No. 2, 2, 1997, p. 91-97.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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T1 - Unique properties of the capacitative Ca(2+)-entry antagonist LU 52396: its inhibitory activity depends on the activation state of the cells.
AU - Guse, A H
AU - de Wit, C
AU - Klokow, T
AU - Schweitzer, K
AU - Mayr, Georg W.
PY - 1997
Y1 - 1997
N2 - The pharmacological properties of the recently described antagonist for capacitative Ca2+ entry LU 52396 were investigated and compared to known Ca2+ antagonists in Jurkat T-lymphocytes. In the first set of experiments, cells were stimulated with the anti-CD3 monoclonal antibody OKT3 and, subsequently, Ca2+ antagonists were added. Under such conditions SK-F 96365, econazole, nitrendipine and ZnCl2 dose-dependently antagonized Ca2+ signaling, whereas LU 52396 in concentrations up to 100 microM did not. In contrast, when LU 52396 was added a few minutes before OKT3, a dose-dependent inhibition of the OKT3-stimulated Ca2+ signals by LU 52396 was observed. Likewise, by prior addition of LU 52396 to thapsigargin-stimulated Jurkat T cells, a dose-dependent inhibition of Ca2+ signals was achieved. The IC50 value of LU 52396 for both agonists was about 5 microM. LU 52396 also inhibited Jurkat T cell proliferation, but showed cytotoxic effects at concentrations > 50 microM. Our data indicate that, in contrast to the other Ca2+ antagonists SK-F 96365, econazole, nitrendipine and ZnCl2, LU 52396 recognized the channel for capacitative Ca2+ entry only when intracellular Ca2+ was low and the channel was in its closed state.
AB - The pharmacological properties of the recently described antagonist for capacitative Ca2+ entry LU 52396 were investigated and compared to known Ca2+ antagonists in Jurkat T-lymphocytes. In the first set of experiments, cells were stimulated with the anti-CD3 monoclonal antibody OKT3 and, subsequently, Ca2+ antagonists were added. Under such conditions SK-F 96365, econazole, nitrendipine and ZnCl2 dose-dependently antagonized Ca2+ signaling, whereas LU 52396 in concentrations up to 100 microM did not. In contrast, when LU 52396 was added a few minutes before OKT3, a dose-dependent inhibition of the OKT3-stimulated Ca2+ signals by LU 52396 was observed. Likewise, by prior addition of LU 52396 to thapsigargin-stimulated Jurkat T cells, a dose-dependent inhibition of Ca2+ signals was achieved. The IC50 value of LU 52396 for both agonists was about 5 microM. LU 52396 also inhibited Jurkat T cell proliferation, but showed cytotoxic effects at concentrations > 50 microM. Our data indicate that, in contrast to the other Ca2+ antagonists SK-F 96365, econazole, nitrendipine and ZnCl2, LU 52396 recognized the channel for capacitative Ca2+ entry only when intracellular Ca2+ was low and the channel was in its closed state.
M3 - SCORING: Zeitschriftenaufsatz
VL - 22
SP - 91
EP - 97
JO - CELL CALCIUM
JF - CELL CALCIUM
SN - 0143-4160
IS - 2
M1 - 2
ER -
