title: Inhibition of the antigen-induced activation of RBL-2H3 cells by charybdotoxin and cetiedil.
abstract: Quinidine and Ba(2+), non-selective K(+)-channel blockers, have previously been shown to inhibit antigen-induced mediator (beta-hexosaminidase) release from RBL-2H3 cells, a mucosal-type mast cell line. We therefore used selective blockers of Ca(2+)-activated and other K(+) channels to determine if there was a role for these channels in antigen-induced mediator release. Charybdotoxin and cetiedil dose-dependently inhibited beta-hexosaminidase release with IC(50) values of 133 nM and 84 microM, respectively. Charybdotoxin also inhibited the repolarization phase of the antigen-induced biphasic change in the membrane potential (IC(50) 84 nM), antigen-stimulated 86Rb(+)-efflux and increase in free intracellular calcium, [Ca(2+)](i). Iberiotoxin, margatoxin, apamin and tetraethylammonium had no effect on beta-hexosaminidase release. These results suggest that K(+) conductances play a significant role in mediator release from RBL-2H3, that these conductances are of the intermediate conductance Ca(2+)-activated K(+) channel (IK(Ca)) type, and that they are somewhat similar to those which have been described in red blood cells, though they are much less sensitive to clotrimazole.
authors.affiliation: Department of Pharmacology, University College London, Gower St., London WC1E 6BT, UK.
authors.forename: Jamshid
authors.initials: J
authors.lastname: Narenjkar
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Marsh
authors.forename: El-Sayed K
authors.initials: el-SK
authors.lastname: Assem
mesh_terms: D000818:Animals; D000941:Antigens / Q000494:pharmacology*; D001381:Azepines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D018999:Charybdotoxin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007546:Isoquinolines / Q000737:chemistry / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism; D011758:Pyrroles / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
chemical_list: C490103:8,9-dimethoxyl-1-(4-methoxy-phenyl)-5,6-dihydro-pyrrolo(2,1-a)isoquinoline-2,3-dione; D000941:Antigens; D001381:Azepines; D007546:Isoquinolines; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011758:Pyrroles; D018999:Charybdotoxin; C006955:cetiedil; D002118:Calcium