Activation of mast cells induced by agonists of proteinase-activated receptors under normal conditions and during acute inflammation in rats.
Functions of thrombin as a modulator of inflammation and tissue repair are mediated by the proteinase-activated receptor (PAR) family. Some of these effects may be induced by activation of mast cells. To characterize the degranulation of rat peritoneal mast cells in response to PAR agonists, the effects of thrombin, trypsin and peptide agonists of PARs (PAR-AP, proteinase-activated receptor-activating peptides) on secretion were investigated. The release of beta-hexosaminidase by thrombin (0.01-1 microM) was concentration-dependent and mediated via PAR(1), as evidenced by cathepsin G (100 microM)-induced inactivation of PAR(1) and thrombin-stimulated PAR(1) desensitization. Trypsin (1 microM) accelerated histamine secretion. The PAR(1)-AP, TRAP (SFFLRN, 1-100 microM) and the PAR(2)-AP SLIGRL (5-100 microM) caused the release of histamine, and beta-hexosaminidase from inflammatory mast cells were obtained from a model of acute peritonitis in rats. Relative to the response to compound 48/80, the thrombin- and TRAP-induced release of beta-hexosaminidase was higher in inflammatory mast cells than in the control. This suggests that additional exposure of PAR(1) on mast cells to PAR agonists or an increase in PARs sensitivity to PAR agonists probably occurred during acute inflammation.
Dugina
Tamara N
TN
Department of Human Physiology, Faculty of Biology, Lomonosov Moscow State University, Moscow 119992, Russia.
Kiseleva
Ekaterina V
EV
Glusa
Erika
E
Strukova
Svetlana M
SM
D000208:Acute Disease; D000818:Animals; D015550:Cell Degranulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000737:chemistry; D007249:Inflammation / Q000503:physiopathology*; D007274:Injections, Intraperitoneal; D007665:Ketotifen / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000493:pharmacokinetics; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010538:Peritonitis / Q000139:chemically induced; D051381:Rats; D017208:Rats, Wistar; D044463:Receptor, PAR-1 / Q000187:drug effects; D044462:Receptors, Proteinase-Activated / Q000819:agonists* / Q000187:drug effects; D018179:Receptors, Thrombin / Q000187:drug effects; D013864:Thioglycolates / Q000008:administration & dosage / Q000009:adverse effects; D013917:Thrombin / Q000008:administration & dosage / Q000493:pharmacokinetics; D014357:Trypsin / Q000008:administration & dosage / Q000493:pharmacokinetics; D001619:beta-N-Acetylhexosaminidases / Q000737:chemistry; D003189:p-Methoxy-N-methylphenethylamine / Q000008:administration & dosage / Q000493:pharmacokinetics
D010446:Peptide Fragments; D044463:Receptor, PAR-1; D044462:Receptors, Proteinase-Activated; D018179:Receptors, Thrombin; D013864:Thioglycolates; D003189:p-Methoxy-N-methylphenethylamine; D006632:Histamine; D001619:beta-N-Acetylhexosaminidases; D014357:Trypsin; D013917:Thrombin; D007665:Ketotifen