Histamine release from beta-escin-permeabilized rat peritoneal mast cells and its inhibition by intracellular Ca2+ blockers, calmodulin inhibitors and cAMP.
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 process leading to histamine release, and (2) cAMP seems to inhibit histamine release, even in the stages following Ca2+ release from the intracellular Ca2+ store.
Izushi
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Tasaka
K
K
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002463:Cell Membrane Permeability / Q000187:drug effects; D000242:Cyclic AMP / Q000494:pharmacology*; D004928:Escin / Q000494:pharmacology*; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects*; D007295:Inositol Phosphates / Q000494:pharmacology; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D012503:Saponins / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002147:Calmodulin; D007295:Inositol Phosphates; D012503:Saponins; D013449:Sulfonamides; D013873:Thionucleotides; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; C017967:W 7; D004928:Escin; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D002118:Calcium