The role of sensorial neuropeptides in the edematogenic responses mediated by B(1) agonist des-Arg(9)-BK in rats pre-treated with LPS.
In the present study we have investigated some of the mechanisms underlying B(1) kinin receptor-induced paw edema formation in rats that had been treated with LPS, paying special attention to the involvement of neurogenic inflammation. Intradermal (i.d.) injection of the B(1) receptor agonist des-Arg(9)-BK (100 nmol/paw) resulted in a marked increase in paw volume in animals pre-treated with LPS (0.40+/-0.06 ml). The co-injection of the selective NK(1) FK888 (1 nmol/paw) or NK(2) SR 48968 (3 nmol/paw) receptor antagonists resulted in a significant inhibition of the edema induced by des-Arg(9)-BK (30+/-4 and 25+/-7%, respectively). The NK(3) SR 142801 (3 nmol/paw) antagonist did not demonstrate any significant effect on B(1) receptor-mediated paw edema. The edema induced by des-Arg(9)-BK was also significantly inhibited (33+/-5%) by the co-injection of the CGRP-receptor antagonist CGRP 8-37 (1 nmol/paw) or by treatment of animals with capsaicin (50 mgkg(-1), s.c., 48 h, prior) (45+/-4%). The pre-treatment of animals with methysergide or with mianserin, 5-HT(1) and 5HT(2) antagonists, respectively (both 10 mgkg(-1), i.p. 30 min), resulted in a significant reduction of the edema mediated by B(1) receptors (23+/-5 and 20+/-3%, respectively). In addition, compound 48/80 (12 microg/paw, 24 h) significantly reduced des-Arg(9)-induced paw edema in rats pre-treated with LPS (23+/-3%), while the treatment of animals with the H(1) receptor antagonist pyrilamine (10 mgkg(-1), i.p., 30 min) failed to affect the edematogenic responses involving B(1) receptors. Finally, the co-injection of NOS inhibitors L-NAME (100 nmol/paw) or 7-NINA (10 nmol/paw) did not affect the rat paw edema caused by des-Arg(9)-BK, whereas they significantly inhibited BK-induced paw edema. Jointly, the results of the present study show that the edematogenic response mediated by the activation of B(1) receptors, in animals pre-treated with LPS, involves the release of tachykinins and CGRP, as well as serotonin, while NO and histamine seem not to be involved. Therefore, these data further support the notion that B(1) receptors have an important role in modulating the inflammatory processes.
Ferreira
P K
PK
Department of Pharmacology, Center of Biological Sciences, Universidade Federal de Santa Catarina, Rua Ferreira Lima, 82, 88015-420, Florianópolis, Brazil.
Campos
M M
MM
Calixto
J B
JB
D000818:Animals; D001549:Benzamides / Q000008:administration & dosage / Q000378:metabolism; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000276:immunology; D015740:Calcitonin Gene-Related Peptide / Q000008:administration & dosage / Q000378:metabolism; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin / Q000008:administration & dosage / Q000378:metabolism; D004487:Edema / Q000139:chemically induced / Q000276:immunology; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology*; D008297:Male; D008784:Methysergide / Q000008:administration & dosage / Q000378:metabolism; D008803:Mianserin / Q000008:administration & dosage / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000378:metabolism; D064729:Neurokinin-1 Receptor Antagonists; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010446:Peptide Fragments / Q000008:administration & dosage / Q000378:metabolism; D010880:Piperidines / Q000008:administration & dosage / Q000378:metabolism; D011720:Pyrazoles / Q000008:administration & dosage / Q000378:metabolism; D011725:Pyridines / Q000008:administration & dosage / Q000378:metabolism; D011738:Pyrilamine / Q000008:administration & dosage / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin / Q000819:agonists*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors; D018042:Receptors, Neurokinin-3 / Q000037:antagonists & inhibitors; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000378:metabolism; D003189:p-Methoxy-N-methylphenethylamine / Q000008:administration & dosage / Q000378:metabolism
D001549:Benzamides; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D006634:Histamine H1 Antagonists; D008070:Lipopolysaccharides; D064729:Neurokinin-1 Receptor Antagonists; D010446:Peptide Fragments; D010880:Piperidines; D011720:Pyrazoles; D011725:Pyridines; D043783:Receptor, Bradykinin B1; D018002:Receptors, Bradykinin; D018041:Receptors, Neurokinin-2; D018042:Receptors, Neurokinin-3; D012702:Serotonin Antagonists; C058636:calcitonin gene-related peptide (8-37); C102861:FK 838; C024626:bradykinin, des-Arg(9)-; D008803:Mianserin; D003189:p-Methoxy-N-methylphenethylamine; C073839:SR 48968; D019001:Nitric Oxide Synthase; D011738:Pyrilamine; D015740:Calcitonin Gene-Related Peptide; C091554:SR 142801; D002211:Capsaicin; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D008784:Methysergide