Inhibitory effects of oxatomide on intracellular Ca mobilization, Ca uptake and histamine release, using rat peritoneal mast cells.
Oxatomide at concentrations of 0.01-10 microM inhibited not only an increase in 45Ca uptake but also the intracellular Ca2+ release induced by compound 48/80 in rat peritoneal mast cells. At higher concentrations, ketotifen or other calcium antagonists caused similar inhibitory effects. However, the inhibitory effect of oxatomide on the 45Ca uptake into rat neonatal heart cells was much weaker than that of verapamil. Through image processing of quin 2-stained mast cells, it was revealed that oxatomide inhibited Ca2+ release from the intracellular store. Although oxatomide alone did not affect cAMP and cGMP contents in sensitized guinea pig lung samples, the drug effectively prevented changes in the nucleotide contents evoked by antigen challenge. These results suggest that the inhibitory effect of oxatomide on histamine release may be caused by a combination of prevention of Ca uptake, which is highly selective toward mast cells; inhibition of Ca2+ release from the intracellular Ca store, and elevation of the cAMP content in mast cells.
D000634:Aminoquinolines; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D007090:Image Interpretation, Computer-Assisted; D007473:Ion Channels / Q000187:drug effects; D007665:Ketotifen / Q000494:pharmacology; D008168:Lung / Q000276:immunology / Q000378:metabolism; D008297:Male; D008407:Mast Cells / Q000187:drug effects*; D008856:Microscopy, Fluorescence / Q000379:methods; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010529:Peritoneal Cavity / Q000166:cytology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D000634:Aminoquinolines; D002132:Calcium Radioisotopes; D006634:Histamine H1 Antagonists; D007473:Ion Channels; D010879:Piperazines; D003189:p-Methoxy-N-methylphenethylamine; D000242:Cyclic AMP; C015408:oxatomide; C035739:Quin2; D002118:Calcium; D007665:Ketotifen