Role of calcium in histamine release from rat mast cells activated by various secretagogues; intracellular calcium mobilization correlates with histamine release.
Anti-IgE, con A or antigen caused an increase in the intracellular calcium concentration, [Ca2+]i, of mast cells. The increase occurred in two stages: a rapid initial rise caused by Ca-mobilization from intracellular Ca-stores and a second sustained rise caused by an influx of extracellular calcium (White, J.R., Pluznik, D.V., Ishizaka, K. & Ishizaka, T. (1985) Proc. Natl. Acad. Sci. U.S.A. 82, 8193-8197). The rapid initial rise was followed by a release of histamine, which seemed to coincide with the second rise. A23187 and compound 48/80 induced a rapid initial rise in [Ca2+]i, followed by a gradual decrease in [Ca2+]i, GMCHA-OPhBut, a specific pH 7 tryptase inhibitor (Muramatu, M., Ito, T., Takei, M. & Endo, K. (1988) Biol. Chem. Hoppe-Seyler 369, 617-625), strongly inhibited both the initial and second rises of [Ca2+]i, as well as histamine release by these secretagogues, and its effects on the initial rise were closely correlated with those on histamine release. Addition of GMCHA-OPhBut immediately after the initial rise strongly inhibited the second rise, thereby decreasing the final [Ca2+]i. These results strongly suggested a possible involvement of pH 7 tryptase, not only in Ca-mobilization leading to the initial rise in [Ca2+]i, but also in the second rise. Trapping of extracellular calcium by 3mM EGTA decreased both the initial rise in [Ca2+]i and histamine secretion induced by anti-IgE or con A; the magnitude of this effect depended on the time between induction and EGTA addition. Histamine release was closely correlated with the initial rise in [Ca2+]i. Similar results were obtained with A23187, but even 5 min after the addition of EGTA an initial rise of [Ca2+]i could still be induced, and histamine (30% of total histamine) was still released. However, A23187 did not induce a rise in [Ca2+]i in mast cells which had been exhaustively washed with Tyrode/Hepes solution containing 3mM EGTA, followed by suspension in the same solution. Even at 20 min after depletion of the extracellular calcium, compound 48/80 still caused an initial rise in [Ca2+]i to above half the maximal value, and histamine secretion was even less affected. The above results indicated that the initial rise in [Ca2+]i, due to Ca-mobilization, correlates with the histamine release promoted by the secretagogues described. On the other hand, isoproterenol strongly induced histamine secretion with no change of [Ca2+]i, while EGTA treatment prior to isoproterenol stimulation had no effect on histamine release, indicating a different secretion mechanism.
Takei
M
M
Faculty of Pharmacy, Tokushima Bunri University.
Urashima
H
H
Endo
K
K
Muramatu
M
M
D000634:Aminoquinolines / Q000502:physiology; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology; D004533:Egtazic Acid / Q000494:pharmacology; D005453:Fluorescence; D006636:Histamine Release / Q000187:drug effects*; D007073:Immunoglobulin E / Q000276:immunology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000378:metabolism*; D051381:Rats; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000634:Aminoquinolines; D000888:Antibodies, Anti-Idiotypic; D003509:Cyclohexanecarboxylic Acids; D007073:Immunoglobulin E; D000001:Calcimycin; D003189:p-Methoxy-N-methylphenethylamine; D004533:Egtazic Acid; C038303:NCO 650; C035738:Quin2-acetoxymethyl ester; D007545:Isoproterenol; D002118:Calcium