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Dual effects of tetrandrine on cytosolic calcium in human leukaemic HL‐60 cells: intracellular calcium release and calcium entry blockade
Author(s) -
Leung YukMan,
Kwan ChiuYin,
Loh TattTuck
Publication year - 1994
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.1476-5381.1994.tb17059.x
Subject(s) - thapsigargin , extracellular , intracellular , channel blocker , calcium , tetrandrine , protein kinase c , chemistry , staurosporine , voltage dependent calcium channel , endocrinology , medicine , biology , biochemistry , pharmacology , kinase
1 Tetrandrine (TET, a Ca 2+ antagonist of Chinese herbal origin) and thapsigargin (TSG, an endoplasmic reticulum Ca 2+ pump inhibitor) concentration‐dependently mobilized Ca 2+ from intracellular stores of HL‐60 cells, with EC 50 values of 20 μ m and 0.8 n m , respectively. After intracellular Ca 2+ release by 30 n m TSG, there was no more discharge of Ca 2+ by TET (100 μ m ), and vice versa . 2 Pretreatments with 100 n m rauwolscine (α 2 ‐adrenoceptor antagonist), 100 n m prazosin (α 1 ‐adreno‐ceptor antagonist), 10 n m phorbol myristate acetate (PMA, a protein kinase C activator) or 100 n m staurosporine (a protein kinase C inhibitor) had no effect on 100 μ m TET‐induced intracellular Ca 2+ release. 3 After intracellular Ca 2+ release by 30 n m TSG in Ca 2+ ‐free medium, readmission of Ca 2+ caused a substantial and sustained extracellular Ca 2+ entry. The latter was almost completely inhibited by 100 μ m TET (IC 50 of 20 μ m ) added just before Ca 2+ readmission. In Ca 2+ ‐containing medium, 30 n m TSG caused a sustained phase of cytosolic Ca 2+ elevation, which could be abolished by 100 μ m TET. TET was also demonstrated to retard basal entry of extracellular Mn 2+ and completely inhibit TSG‐stimulated extracellular Mn 2+ entry. 4 TSG‐induced extracellular Ca 2+ entry was insensitive to the L‐type Ca 2+ channel blocker, nifedipine (1 μ m ), but was completely inhibited by the non‐selective Ca 2+ channel blocker La 3+ (300 μ m ). Depolarization with 100 m m KCl did not raise the cytosolic Ca 2+ level. 5 These data suggest that (a) TET and TSG mobilized the same Ca 2+ pool and TET‐induced intracellular Ca 2+ release was independent of protein kinase C activity and a‐adrenoceptor activation, and (b) TET blocked the voltage‐insensitive Ca 2+ entry pathway activated by TSG. These dual effects on HL‐60 cells were also observed with hernandezine (HER), a TET‐like compound and in another cell type, murine B lymphoma M12.4 cells.