title: Inhibition of the antigen-induced activation of RBL-2H3 cells by cetiedil and some of its analogues.
abstract: Our previous studies on rat basophilic leukaemia (RBL-2H3) cells suggested that IK(Ca) channels similar to those in red blood cells (RBC) may be involved in the antigen-induced beta-hexosaminidase release. Since cetiedil blocks these channels in both cell types, we studied the inhibition by a selection of the synthetic analogues of cetiedil (UCL compounds) of antigen-induced beta-hexosaminidase release and 86Rb(+)-efflux from RBL-2H3 cells. We tested the (+)- and (-)-enantiomers of cetiedil (UCL 1348 and UCL 1349), the more lipophilic triphenylacetic acid derivatives (UCL 1495 and UCL 1617) and (9-benzyl-fluoren)-9-yl derivatives (UCL 1608 and UCL 1710). They all inhibited antigen-induced beta-hexosaminidase release and 86Rb(+)-efflux. Their relative potency in inhibiting antigen-induced beta-hexosaminidase release was UCL 1608>1710>1617>1348>1349>1495, with IC(50) values of 9.6+/-0.6, 14.4+/-2.2, 23.4+/-1.4, 29.8+/-1.1, 77.5+/-11.8 and 104.6+/-14.7 (microM), respectively. These IC(50)s suggest some dissimilarity between IK(Ca) in RBL-2H3 cells and RBC. Lipophilicity and potency were well correlated in RBC, but not in RBL-2H3 cells.
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: El-Sayed K
authors.initials: el-SK
authors.lastname: Assem
authors.forename: C Robin
authors.initials: CR
authors.lastname: Ganellin
mesh_terms: D000818:Animals; D000941:Antigens / Q000494:pharmacology*; D001381:Azepines / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats
chemical_list: D000941:Antigens; D001381:Azepines; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; C006955:cetiedil