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Calcium‐pH crosstalks in rat mast cells: cytosolic alkalinization, but not intracellular calcium release, is a sufficient signal for degranulation
Author(s) -
Alfonso A,
Cabado A G,
Vieytes M R,
Botana L M
Publication year - 2000
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 - 10.1038/sj.bjp.0703490
Subject(s) - thapsigargin , nigericin , calcium , intracellular , calcium in biology , histamine , cytosol , chemistry , exocytosis , ionomycin , fura 2 , biophysics , biochemistry , microbiology and biotechnology , biology , endocrinology , secretion , organic chemistry , membrane , enzyme
The aim of this work was to study the relationship between intracellular alkalinization, calcium fluxes and histamine release in rat mast cells. Intracellular alkalinization was induced by nigericin, a monovalent cation ionophore, and by NH 4 Cl (ammonium chloride). Calcium cytosolic and intracellular pH were measured by fluorescence digital imaging using Fura‐2‐AM and BCECF‐AM. In rat mast cells, nigericin and NH 4 Cl induce a dose‐dependent intracellular alkalinization, a dose‐dependent increase in intracellular calcium levels by releasing calcium from intracellular pools, and an activation of capacitative calcium influx. The increase in both intracellular calcium and pH activates exocytosis (histamine release) in the absence of external calcium. Under the same conditions, thapsigargin does not activate exocytosis, the main difference being that thapsigargin does not alkalinize the cytosol. After alkalinization, histamine release is intracellular‐calcium dependent. With 2.5 m M EGTA and thapsigargin the cell response decreases by 62%. The cytosolic alkalinization, in addition to the calcium increase it is enough signal to elicit the exocytotic process in rat mast cells.British Journal of Pharmacology (2000) 130 , 1809–1816; doi: 10.1038/sj.bjp.0703490