Mechanism of ketotifen action in hypersensitivity reactions. Its effect on cellular enzymatic activities.
In this study we observed that asthmatics had less methyltransferase activity and greater phosphodiesterase activity than healthy individuals. These enzymatic activities were nearer to values obtained in healthy individuals when we preincubated cells with ketotifen. The modulator effect of this drug on these two enzymes permits, on the one hand, to re-establish the beta-receptor numbers expressed on the membrane, and on the other hand, to inhibit mediator secretion provoked by antigenic stimulus. With its action on adenylate cyclase and phosphodiesterase activities, it allows cAMP intracellular accumulation and hinders the secretory process. Through its action on methyltransferase activity, it is responsible for the normalization of beta-receptor expression observed in asthmatic patients treated with ketotifen.
Castillo
J G
JG
Departamento de Alergología e Inmunología Clínica, Clínica Universitaria, Facultad de Medicina, Universidad de Navarra, Pamplona, Spain.
Oehling
A
A
Gamboa
P M
PM
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000097:blood; D000262:Adenylyl Cyclases / Q000097:blood; D001249:Asthma / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007665:Ketotifen / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D008780:Methyltransferases / Q000097:blood; D008954:Models, Biological; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism
D011943:Receptors, Adrenergic, beta; D008780:Methyltransferases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000262:Adenylyl Cyclases; D002118:Calcium; D007665:Ketotifen