Interactive contribution of NK₁ and kinin receptors to the acute inflammatory oedema observed in response to noxious heat stimulation: studies in NK₁ receptor knockout mice

Abstract

Scald injury in Sv129+C57BL/6 mice induced a temperature and time dependent oedema formation as calculated by the extravascular accumulation of [125I]‐albumin. Oedema formation was suppressed in NK1 knockout mice compared to wildtypes at 10 (P<0.01) and 30 min (P<0.001). However, at 60 min a similar degree of extravasation was observed in the two groups. Kinin B1 (des‐Arg10 Hoe 140; 1 μmol kg−1) and B2 (Hoe 140; 100 nmol kg−1) antagonists caused an inhibition of oedema in wildtype mice at 10 and 30 min (P<0.001), but not at 60 min or at 30 min in NK1 receptor knockout mice. The inhibition of thermic oedema by des‐Arg10 Hoe 140 was reversed by des‐Arg9 bradykinin (0.1 μmol kg−1; P<0.01) and also observed with a second B1 receptor antagonist (des‐Arg9 Leu8 bradykinin; 3 μmol kg−1; P<0.01). Furthermore des‐Arg10 Hoe 140 had no effect on capsaicin (200 μg ear−1) ear oedema, but this was significantly reduced with Hoe 140 (P<0.05). Scalding induced a large neutrophil accumulation at 4 h, as assessed by myeloperoxidase assay (P<0.001). This was not suppressed by NK1 receptor deletion or kinin antagonists. These results confirm an essential role for the NK1 receptor in mediating the early, but not the delayed phase of oedema formation or neutrophil accumulation in response to scalding. The results also demonstrate a pivotal link between the kinins and sensory nerves in the microvascular response to burn injury, and for the first time show a rapid involvement of the B1 receptor in murine skin. British Journal of Pharmacology (2001) 134, 1805–1813; doi:

Antinociceptive Pharmacology ofN-[[4-(4,5-Dihydro-1H-imidazol-2-yl)phenyl]methyl]-2-[2-[[(4-methoxy-2,6-dimethylphenyl) sulfonyl]methylamino]ethoxy]-N-methylacetamide, Fumarate (LF22-0542), a Novel Nonpeptidic Bradykinin B1Receptor Antagonist

“…In contrast to studies of acute nociception, numerous studies have shown that B 1 antagonists are antihyperalgesic in animal models of persistent inflammation (Perkins et al, 1993;Bélichard et al, 2000;Rawlingson et al, 2001), as well as in persistent visceral pain (Jaggar et al, 1998). Des-Arg 9 -[Leu 8 ]-BK, a B 1 receptor antagonist (Marceau and Regoli, 2004) inhibits carrageenan-induced hyperalgesia and formalin-induced paw flick (Rupniak et al, 1997), as well as edema and hyperalgesia associated with burn injuries (Perkins et al, 1993;Rawlingson et al, 2001).…”

“…Des-Arg 9 -[Leu 8 ]-BK, a B 1 receptor antagonist (Marceau and Regoli, 2004) inhibits carrageenan-induced hyperalgesia and formalin-induced paw flick (Rupniak et al, 1997), as well as edema and hyperalgesia associated with burn injuries (Perkins et al, 1993;Rawlingson et al, 2001). LF22-0542 also showed activity in models of inflammatory pain including significant antihyperalgesic actions in the second phase of the formalin response in both mice and rats and in both acute (carrageenan) and persistent (CFA) inflammatory pain.…”

Evidence for the Involvement of the Cannabinoid CB2 Receptor and Its Endogenous Ligand 2-Arachidonoylglycerol in 12-O-Tetradecanoylphorbol-13-acetate-induced Acute Inflammation in Mouse Ear

“…Measurement of Myeloperoxidase Activity in Mouse Ear-Myeloperoxidase (MPO), located in the azurophilic granules of neutrophils, has been used as an enzyme marker of neutrophil infiltration into inflamed tissues (45). MPO activity in the mouse ear was estimated as described in Ref.…”

SSR240612 [(2R)-2-[((3R)-3-(1,3-Benzodioxol-5-yl)-3-{[(6-methoxy-2-naphthyl)sulfonyl]amino}propanoyl)amino]-3-(4-{[2R,6S)-2,6-dimethylpiperidinyl]methyl}phenyl)-N-isopropyl-N-methylpropanamide Hydrochloride], a New Nonpeptide Antagonist of the Bradykinin B1Receptor: Biochemical and Pharmacological Characterization

“…The therapeutic interest of B 1 receptor blockage is supported further by the pharmacological properties of B 1 peptide antagonists. Edema and hyperalgesia associated to burn injuries are attenuated by desArg 9 ,Leu 8 -BK Rawlingson et al, 2001). The peptide inhibitor R-954 was shown to reduce eosinophil and neutrophil infiltration and airway hyperreactivity induced by lung inflammation (Gama Landgraf et al, 2003).…”