[The role of PAR1 in the protective action of activated protein C in the non-immune mast cell activation].
Activated protein C (APC) regulates the functional activity of mast cells by reducing release of beta-hexosaminidase, the marker of mast cell degranulation. APC could modulate the cell secretion of both: the rest mast cells and the activated cells with degranulators, such as proteinase-activated receptor agonist peptide (PAR1-AP) and compound 48/80. PAR1 desensitization with thrombin abolishes the effect of low APC concentration (< or =1,5 nM) on beta-hexosaminidase release by mast cells. APC, inactivated with phenilmethylsulfonilftoride (PMSF), did non mimic the enzyme action on mast cells. The duodenal proteinase, duodenase, activates the peritoneal mast cell via PAR1. APC abolishes the proinflammatory action of duodenase and PAR1-AP by means of reducing release of mast cell mediators. Pretreatment of mast cell with L-NAME abolished these APC effects. Thus, APC-induced decrease of mediator release could be attributed to NO generation by mast cells. Our data indicate that PAR1 takes part in the mechanism of regulatory anti-inflammatory APC action.
Makarova
A M
AM
Gorbacheva
L R
LR
Zamolodchikova
T S
TS
Rumsh
L D
LD
Smirnov
M
M
Strukova
S M
SM
D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D010529:Peritoneal Cavity / Q000166:cytology; D011486:Protein C / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000819:agonists / Q000502:physiology*; D012697:Serine Endopeptidases / Q000378:metabolism; D015398:Signal Transduction; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
D009842:Oligopeptides; C462999:PAR-1-activating peptide; D011486:Protein C; D044463:Receptor, PAR-1; D009569:Nitric Oxide; D003189:p-Methoxy-N-methylphenethylamine; D012697:Serine Endopeptidases; C078261:duodenase; D019331:NG-Nitroarginine Methyl Ester