Effect on mast cell histamine of inhibiting histamine formation in vivo with alpha-fluoromethylhistidine.
An irreversible inhibitor of histidine decarboxylase, alpha-fluoromethylhistidine (FMH), was used to inhibit histamine formation by mast cells in vivo. Even at doses of FMH sufficient to reduce histamine formation more than 95%, the ability of mast cells to synthesize histamine recovered rapidly. It was possible, however, to sustain levels of histamine-forming activity below 10% of normal with continuous administration of FMH from subcutaneously implanted osmotic pumps. Administration of FMH under these conditions did not deplete significantly mast cell histamine but did prevent the increase in total mast cell histamine that occurs over 14 days and also prevented the reconstitution of mast cell histamine stores after depletion by treatment with polymyxin B.
D000818:Animals; D002262:Carboxy-Lyases / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000096:biosynthesis / Q000378:metabolism*; D006639:Histidine / Q000031:analogs & derivatives*; D006640:Histidine Decarboxylase / Q000037:antagonists & inhibitors*; D007263:Infusions, Parenteral / Q000295:instrumentation; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism*; D008762:Methylhistidines / Q000008:administration & dosage / Q000494:pharmacology*; D010529:Peritoneal Cavity; D011112:Polymyxin B / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors
D008762:Methylhistidines; D006639:Histidine; C028309:alpha-fluoromethylhistidine; D006632:Histamine; D002262:Carboxy-Lyases; D006640:Histidine Decarboxylase; D011112:Polymyxin B