[Duodenase activates rat peritoneal mast cells via protease-activated receptors of type 1].
It was found that duodenase, a serine protease from the bovine duodenum, activates rat peritoneal mast cells (PMC) in vitro presumably via protease-activated receptors (PARs). Like thrombin (a serine protease from the blood coagulation system) and the PAR1 agonist peptide (PAR1-AP), duodenase was shown to accelerate the secretion of beta-hexosaminidase (a marker of cell degranulation) by PMC in a dose-dependent manner. The blockage of the proteolytic activity of duodenase toward the substrate Tos-Gly-Pro-Lys-pNA by the soybean Bauman-Birk protease inhibitor substantially reduced (by 40%) the ability of duodenase to stimulate the secretory activity of PMC. Pretreatment of PMC with duodenase decreased the beta-hexosaminidase secretion induced by thrombin and PAR1-AP by 35 and 41.7%, respectively, and abolished the antiinflammatory effect of activated protein C. At the same time, pretreatment of PMC with duodenase did not affect the secretion of beta-hexosaminidase induced by compound 48/80, a nonspecific degranulator of mast cells. Duodenase, unlike PAR1-AP (30-100 microM), in a broad concentration range (10-100 nM) did not induce aggregation of human platelets, but suppressed the platelet aggregation elicited by PAR1-AP.
Makarova
A M
AM
Zamolodchikova
T S
TS
Rumsh
L D
LD
Strukova
S M
SM
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects; D002417:Cattle; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D009842:Oligopeptides / Q000737:chemistry; D010447:Peptide Hydrolases / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010537:Peritoneum / Q000276:immunology*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000819:agonists*; D012697:Serine Endopeptidases / Q000737:chemistry / Q000494:pharmacology*; D013917:Thrombin / Q000494:pharmacology; D001619:beta-N-Acetylhexosaminidases / Q000032:analysis / Q000378:metabolism
D009842:Oligopeptides; D010455:Peptides; D044463:Receptor, PAR-1; C014413:chromozym TH; D001619:beta-N-Acetylhexosaminidases; D010447:Peptide Hydrolases; D012697:Serine Endopeptidases; C078261:duodenase; D013917:Thrombin