title: Inhibition of IgE-mediated histamine release from rat basophilic leukemia cells and rat mast cells by inhibitors of transmethylation.
abstract: This study evaluated the effect of inhibitors of transmethylation on histamine release from rat mast cells and rat basophilic leukemia cells. IgE-mediated histamine release from rat basophilic leukemia cells (RBL-2H3 cells) was inhibited by 3-deazaadenosine (DZA) in the presence of L-homocysteine thiolactone (Hcy) or the combination of adenosine, erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA), and Hcy in a dose-dependent fashion. There were no significant changes in the cellular cAMP levels by these inhibitors. Histamine release induced by anti-IgE or dextran from normal rat mast cells was also blocked by DZA plus Hcy in a dose-dependent manner. DZA at 10(-3) M in the presence of 10(-4) M Hcy or the combination of 10(-3) M adenosine, 10(-4) M EHNA, and 10(-3) M Hcy inhibited lipid (perhaps phospholipid) methylation into RBL-2H3 cells without affecting choline incorporation. In the presence of 10(-3) M DZA plus 10(-4) M Hcy there was a 170-fold increase in [35S]AdoHcy with the concomitant appearance of 3-deaza-AdoHcy when the cells were incubated with [35S]methionine, thus indicating that these drugs inhibited methylation reaction(s) through the intracellular accumulation of AdoHcy and 3-deaza-AdoHcy. In contrast, histamine release from rat mast cells induced by the calcium ionophore A23187, compound 48/80, polymyxin B, or ATP was not inhibited by these compounds. These results suggest that IgE- or dextran-mediated histamine release involves methylation reactions(s), whereas the other secretagogues bypass this early step.
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D001491:Basophils; D005260:Female; D006636:Histamine Release / Q000187:drug effects*; D006710:Homocysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D007073:Immunoglobulin E / Q000378:metabolism*; D007938:Leukemia / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology; D008745:Methylation; D051379:Mice; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012435:S-Adenosylhomocysteine / Q000494:pharmacology; D012436:S-Adenosylmethionine / Q000494:pharmacology; D014372:Tubercidin / Q000494:pharmacology
chemical_list: C018258:3-deazaadenosine; D006710:Homocysteine; D007073:Immunoglobulin E; C010192:9-(2-hydroxy-3-nonyl)adenine; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; C007957:homocysteine thiolactone; D000225:Adenine; D000241:Adenosine; D014372:Tubercidin