Ketotifen effect on secretion of histamine from basophils and on proliferative response of mononuclear cells of human peripheral blood.
Within the concentrations tested (0.125-1 mM), Ketotifen KT did not release histamine from the basophils, but, depending on dosage, inhibited release induced by anti-IgE antibodies or Con A. KT action developed without a latent period and was maintained for all time intervals used in the experiments (up to 40 min). Cell washing for histamine resulted in a rapid (not longer than 5 min) recovery of their sensitivity to histamine releasers. KT did not affect histamine release induced by cytotoxic releasers (chlorpromazine and melittin). In low concentrations (5 and 50 microM), KT potentiated mononuclear cell (MNC) response to phytohemagglutinin (PHA) evaluated by 3H-thymidine incorporation, and, in high concentrations, blocked it. In doses blocking the proliferative response to PHA, KT also blocked MNC proliferation induced by Con and PWM. Within the tested concentrations, KT inhibited the PHA-induced increase of MNC protein synthesis evaluated by 14C-L-leucine incorporation, and, in high concentrations-blocked it. The obtained findings show that KT does not affect the induction stages of the proliferative response, but rather the stages preceding the cells transmission into the "S-phase". KT action was accompanied by a change in the cells electrophoretic mobility (EPM): in low concentrations (5 microM) KT was found to intensify the cells EPM and in high ones (250-500 microM)-to inhibit the EPM of MNC.
Gushchin
I S
IS
Serov
A A
AA
Zebrev
A I
AI
Sapozhnihov
A M
AM
Khristenko
A V
AV
D000328:Adult; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D001491:Basophils / Q000187:drug effects* / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects; D002746:Chlorpromazine / Q000494:pharmacology; D004261:DNA Replication / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D005260:Female; D006636:Histamine Release / Q000187:drug effects*; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D007665:Ketotifen / Q000494:pharmacology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D008555:Melitten / Q000494:pharmacology; D008934:Mitogens / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects*; D014176:Protein Biosynthesis; D011506:Proteins / Q000037:antagonists & inhibitors
D000888:Antibodies, Anti-Idiotypic; D008934:Mitogens; D011506:Proteins; D008555:Melitten; D007073:Immunoglobulin E; D002746:Chlorpromazine; D007665:Ketotifen