Effects of an inhibitor of microsomal Ca2+ ATPase, 2,5-di(tert-butyl)-1,4-hydroquinone on intracellular free Ca2+ level and histamine secretion in rat basophilic leukemia cells

• Published in: Japanese Journal of Pharmacology Vol. 67; no. suppl.2; p. 289
• Main Authors: Kitajima, Satoshi, Momma, Junto, Tsuda, Mitsuhiro, Kurokawa, Yuji, Teshima, Reiko, Sawada, Jun-ichi
• Format: Journal Article
• Language: English
• Published: The Japanese Pharmacological Society 1995
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)47121-7

We examined the effect of the inhibitor of microsomal Ca2+ ATPase, 2,5-di(tert-butyl)-1,4-hydroquinone (DtBHQ) on intracellular free Ca2+ level (「Ca2+ 」_i ) and histamine secretion in rat basophilic leukemia (RBL-2H3) cells. DtBHQ (0.1 - 10 μM) alone induced rapid and sustained increases in 「Ca^2+ 」_i in a concentration-dependent manner. In cells sensitized with anti-dinitrophenol IgE, DtBHQ (10 μM) further increased the antigen (dinitrophenylated BSA)-induced Ca^2+ response. In the absence of external Ca^2+ (with 1 mM EGTA), both DtBHQ (10 μM) and the antigen (10 μg/ml) induced transient increases in 「Ca^2+ 」_i . Even after the antigen-induced response, DtBHQ elicited a transient increase in 「Ca^2+ 」_i while the antigen was ineffective following the DtBHQ-induced response. In sensitized cells, both DtBHQ (10 μM) and antigen (10 μg/ml) elicited histamine secretion although the response was far stronger in the latter case. The DtBHQ (10 μM)-induced histamine secretion was markedly enhanced by the addition of either the antigen (10 μg/ml) or the protein kinase C activator, phorbol 12-myristate 13-acetate (TPA) (10 ng/ml), TPA alone not causing an increase. These results suggest that DtBHQ increases 「Ca^2+ 」_i through both Ca^2+ influx and Ca^2+ release from intracellular Ca^2+ storage sites and support the idea that Ca^2+ signals are necessary but not sufficient for histamine secretion in RBL-2H3 cells.