Collagenase-induced oedema in the rat paw and the kinin system.
Collagenase (100 micrograms) induced a large plasma extravasation, during the first 15 min after its injection in rat paw, associated with the rapid development of oedema which subsided after 6 h. The extent of the oedema was similar in normal and kininogen-deficient rats. The swelling induced in normal rats was reduced by HOE 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]bradykinin), a bradykinin B2 receptor antagonist, and by three serine protease inhibitors, soybean trypsin inhibitor (SBTI), Leucaena leucocephala trypsin inhibitor 1 (LLTI-1) and Leucaena leucocephala trypsin inhibitor 2 (LLTI-2). These agents had no effect on the oedema induced in kininogen-deficient rats. The swelling was also reduced by methysergide, indomethacin, ketoprofen and methylprednisolone. It was increased by heparin, but it was not modified by mepyramine, WEB 2086 (3-[4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f][1,2,4]-triazolo- [4,3-a][1,4]-diazepine-2-yl]-1-(4-morpholinyl)-1-propanone) and NG-nitro-L-arginine. In vitro, collagenase did not release kinins from rat plasma or from purified T-kininogen. LLTI-1 and LLTI-2 did not inhibit collagenase activity for one of its specific substrates. Kinins are thus involved in the development of collagenase oedema in normal rats. Their generation would be indirect following changes in matrix proteins in extravascular spaces. Nevertheless, kinins are not the decisive mediators of the swelling. Serotonin, possibly released from platelets, and prostanoids participate in the inflammatory process.
Souza Pinto
J C
JC
Department of Human Physiology, University of Liège, Belgium.
Remacle-Volon
G
G
Sampaio
C A
CA
Damas
J
J
D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D001381:Azepines / Q000008:administration & dosage / Q000494:pharmacology; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017364:Collagenases / Q000008:administration & dosage / Q000633:toxicity*; D004487:Edema / Q000139:chemically induced* / Q000378:metabolism; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000633:toxicity; D006614:Hindlimb; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D016234:Kallikrein-Kinin System / Q000187:drug effects / Q000502:physiology*; D007660:Ketoprofen / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007704:Kininogens / Q000172:deficiency; D008297:Male; D008784:Methysergide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D019335:Nitroarginine; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D011738:Pyrilamine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D014230:Triazoles / Q000008:administration & dosage / Q000494:pharmacology
D001381:Azepines; D007704:Kininogens; D010975:Platelet Aggregation Inhibitors; D015842:Serine Proteinase Inhibitors; D014230:Triazoles; C052518:WEB 2086; D019335:Nitroarginine; C065679:icatibant; D006493:Heparin; D007660:Ketoprofen; D001120:Arginine; D017364:Collagenases; D011738:Pyrilamine; D001920:Bradykinin; D007213:Indomethacin; D008784:Methysergide