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The role of sensorial neuropeptides in the edematogenic responses mediated by B(1) agonist des-Arg(9)-BK in rats pre-treated with LPS.
- Source :
-
Regulatory peptides [Regul Pept] 2000 May 10; Vol. 89 (1-3), pp. 29-35. - Publication Year :
- 2000
-
Abstract
- 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.
- Subjects :
- Animals
Benzamides administration & dosage
Benzamides metabolism
Bradykinin administration & dosage
Bradykinin immunology
Calcitonin Gene-Related Peptide administration & dosage
Calcitonin Gene-Related Peptide metabolism
Calcitonin Gene-Related Peptide Receptor Antagonists
Capsaicin administration & dosage
Capsaicin metabolism
Edema chemically induced
Edema immunology
Histamine H1 Antagonists administration & dosage
Histamine H1 Antagonists metabolism
Lipopolysaccharides administration & dosage
Male
Methysergide administration & dosage
Methysergide metabolism
Mianserin administration & dosage
Mianserin metabolism
NG-Nitroarginine Methyl Ester administration & dosage
NG-Nitroarginine Methyl Ester metabolism
Neurokinin-1 Receptor Antagonists
Nitric Oxide Synthase antagonists & inhibitors
Peptide Fragments administration & dosage
Peptide Fragments metabolism
Piperidines administration & dosage
Piperidines metabolism
Pyrazoles administration & dosage
Pyrazoles metabolism
Pyridines administration & dosage
Pyridines metabolism
Pyrilamine administration & dosage
Pyrilamine metabolism
Rats
Rats, Wistar
Receptor, Bradykinin B1
Receptors, Neurokinin-2 antagonists & inhibitors
Receptors, Neurokinin-3 antagonists & inhibitors
Serotonin Antagonists administration & dosage
Serotonin Antagonists metabolism
p-Methoxy-N-methylphenethylamine administration & dosage
p-Methoxy-N-methylphenethylamine metabolism
Bradykinin analogs & derivatives
Lipopolysaccharides immunology
Receptors, Bradykinin agonists
Subjects
Details
- Language :
- English
- ISSN :
- 0167-0115
- Volume :
- 89
- Issue :
- 1-3
- Database :
- MEDLINE
- Journal :
- Regulatory peptides
- Publication Type :
- Academic Journal
- Accession number :
- 10771310
- Full Text :
- https://doi.org/10.1016/s0167-0115(00)00094-x