Effect of the tachykinin receptor antagonists, SR 140333, FK 888, and SR 142801, on capsaicin-induced mouse ear oedema.
We examined the effect of SR 140333, a nonpeptide NK1 receptor antagonist, FK 888, a peptide NK1 antagonist, and SR 142801, a non-peptide NK3 antagonist, on ear oedema induced by topical application of capsaicin (250 micrograms/ear) in mice. SR 140333 (ED50:39 micrograms/kg, i.v.) dose-dependently inhibited the oedema response to capsaicin, whereas FK 888 (1.0 mg/kg, i.v.) and SR 142801 (3.0 mg/kg, i.v.) had no effect. Furthermore, SR 140333 significantly (p < 0.001) suppressed ear oedema in response to intradermal injection of substance P (SP) (100 pmol/site) by i.v. administration (0.1 mg/kg,) and co-injection (50 pmol/site). In contrast, FK 888 (1.0 mg/kg, i.v. and 500 pmol/site) was ineffective in the response to SP. The present results suggest that the difference in effects of the two NK1 receptor antagonists on the oedema response to capsaicin is due to species differences in affinities for the NK1 receptor in the mouse skin. Moreover, it seems unlikely that the NK3 receptor is involved primarily in capsaicin-induced mouse ear oedema.
Inoue
H
H
Research Laboratory, Minophagen Pharmaceutical Co., Kanagawa, Japan.
Nagata
N
N
Koshihara
Y
Y
D000818:Animals; D001665:Binding Sites; D002211:Capsaicin / Q000008:administration & dosage / Q000633:toxicity; D004151:Dipeptides / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004427:Ear Diseases / Q000188:drug therapy; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy*; D007211:Indoles / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D007275:Injections, Intravenous; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011812:Quinuclidines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D018039:Receptors, Tachykinin / Q000037:antagonists & inhibitors*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013373:Substance P / Q000008:administration & dosage / Q000633:toxicity
D004151:Dipeptides; D007211:Indoles; D010880:Piperidines; D011812:Quinuclidines; D018039:Receptors, Tachykinin; C078949:FK 888; C085215:SR 140333; D013373:Substance P; C091554:SR 142801; D002211:Capsaicin