Abstract
In order to study the intracellular events leading to histamine release, rat peritoneal mast cells were permeabilized using beta-escin, a triterpenoid. IP3 (0.5-10 microM) dose-dependently elicited significant histamine release from permeabilized mast cells in a Ca2+-free medium, as did GTP-gamma-S at concentrations higher than 5 microM, GTP-gamma-S induced IP3 production dose-dependently in association with histamine release. Histamine release induced by IP3 and GTP-gamma-S was inhibited by pretreatment with TMB-8, while neomycin pretreatment suppressed histamine release caused by GTP-gamma-S but not that caused by IP3.IP3 may cause Ca2+ release from the intracellular Ca2+ store as the key event leading to histamine release. At concentrations higher than 0.1 microM, Ca2+ dose-dependently induced histamine release. Both IP3-and Ca2+-induced histamine release from permeabilized mast cells was inhibited by pretreatment with calmodulin inhibitors (W-7 and calmidazolium), or with cytochalasin D or colchicine. Pretreatment with cAMP also inhibited the histamine release induced by either IP3 or Ca2+. From the present study, it can be assumed that (1) Ca2+ may act on a calmodulin-associated process(es) and cytoskeletal systems, in the...Continue Reading
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