NK1 receptors mediate tachykinin-induced plasma extravasation in the rat knee joint.
The tachykinin receptor type that mediates tachykinin-induced plasma extravasation in the rat knee joint was identified by using selective antagonists as well as natural or synthetic agonists. Substance P (SP) and neurokinin (NK) A induced plasma extravasation with almost the same potency and the maximum response was obtained at 5 nmol/knee. NKB was about ten times less potent than SP or NKA. The NK1 selective agonist, [Sar9, Met(O2)11]-SP, was about ten times more potent than SP, and the NK2 selective agonist, [Nle10]-NKA4-10, was about fifty times less potent than NK1 agonist. The NK3 agonist, Senktide, was totally ineffective at 0.5-50 nmol/knee. All responses induced by SP (5 nmol/knee), NKA (5 nmol/knee), NKB (50 nmol/knee), NK1 agonist (0.5 nmol/knee) or NK2 agonist (25 nmol/knee) were significantly and profoundly inhibited by the NK1 selective antagonist, RP67580, but not by the NK2 selective antagonist, SR48968. Taken together, we conclude that tachykinin-induced plasma extravasation in the rat knee joint is mediated via NK1 receptors.
Hirayama
Y
Y
Pharmacological Research Laboratory, Fujisawa Pharmaceutical Co. Ltd., Osaka, Japan.
Yasumitsu
R
R
Kawamura
A
A
Fujii
T
T
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D002199:Capillary Permeability / Q000502:physiology*; D005070:Evans Blue; D006614:Hindlimb / Q000098:blood supply; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D007596:Joints / Q000098:blood supply*; D008297:Male; D015288:Neurokinin A / Q000037:antagonists & inhibitors; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018040:Receptors, Neurokinin-1 / Q000502:physiology*; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors / Q000502:physiology; D013373:Substance P / Q000037:antagonists & inhibitors; D013582:Synovial Fluid / Q000378:metabolism; D015320:Tachykinins / Q000494:pharmacology*
D001549:Benzamides; D007211:Indoles; D054833:Isoindoles; D064729:Neurokinin-1 Receptor Antagonists; D010880:Piperidines; D018040:Receptors, Neurokinin-1; D018041:Receptors, Neurokinin-2; D015320:Tachykinins; C071693:7,7-diphenyl-2-(1-imino-2-(2-methoxyphenyl)ethyl)perhydroisoindol-4-one; D013373:Substance P; D005070:Evans Blue; C073839:SR 48968; D015288:Neurokinin A