Inhibition of the antigen-induced activation of RBL-2H3 cells by charybdotoxin and cetiedil

• Published in: European journal of pharmacology Vol. 483; no. 2; pp. 95 - 106
• Main Authors: Narenjkar, Jamshid, Marsh, Stephen J., Assem, El-Sayed K.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 12-01-2004; Elsevier
• Subjects: Animals; Antigens - pharmacology; Azepines - pharmacology; Biological and medical sciences; Calcium - metabolism; Cell Line, Tumor; Cetiedil; Charybdotoxin; Charybdotoxin - pharmacology; Dose-Response Relationship, Drug; Isoquinolines - chemistry; Isoquinolines - pharmacology; K + channel blocker; Mast Cells - drug effects; Mast Cells - metabolism; Mast Cells - physiology; Mediator secretion; Medical sciences; Membrane Potentials - drug effects; Membrane Potentials - physiology; Pharmacology. Drug treatments; Potassium Channel Blockers - pharmacology; Potassium Channels, Calcium-Activated - antagonists & inhibitors; Potassium Channels, Calcium-Activated - metabolism; Pyrroles - chemistry; Pyrroles - pharmacology; Rats; RBL-2H3 cell; RBL-2H3 cell; Mediator secretion; Cetiedil; Charybdotoxin; K + channel blocker; Vasodilator agent; Secretion; Bronchodilator; K+ channel blocker; Ionic channel; Inorganic element; Potassium
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2003.10.013

Quinidine and Ba
2+, non-selective K
+-channel blockers, have previously been shown to inhibit antigen-induced mediator (β-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 β-hexosaminidase release with IC
50 values of 133 nM and 84 μM, 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 β-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.