Compound 48/80-induced secretion of histamine from rat peritoneal mast cells depends on a tryptase controlled step also leading to chymase activity.
Compound 48/80 caused activation of rat mast cell tryptase and chymase along with the release of histamine. Following low speed centrifugation, tryptase remained essentially in the supernatant while chymase sedimented. Enzyme activities as well as histamine release were inhibited by phenylmethyl-sulfonyl fluoride and tosyl-lysine chloromethyl ketone, which are respectively unspecific and specific inhibitors of trypsin-like enzymes. Chymostatin inhibited chymase, but not the release of histamine by 48/80. Tryptase activity thus seems to be essentially involved in the mechanism of histamine release, while chymase activity may be merely one of its accompanying events.
Department of Pharmacology, Faculty of Medicine, University of São Paulo, Ribeirão Preto, Brazil.
C S
CS
Vassimon
A M
AM
Rothschild
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology; D053818:Chymases; D004789:Enzyme Activation / Q000187:drug effects; D006636:Histamine Release / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012697:Serine Endopeptidases / Q000378:metabolism*; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology*
D011480:Protease Inhibitors; D003189:p-Methoxy-N-methylphenethylamine; D010447:Peptide Hydrolases; C023073:tosylarginine methyl ester hydrolase; D012697:Serine Endopeptidases; D053818:Chymases