Receptor mediation and nociceptin inhibition of bradykinin-induced plasma extravasation in the knee joint of the rat.
OBJECTIVE
The aim was to investigate the signaling mechanisms and regulation of bradykinin (BK)-induced inflammation in rat knee joint.


METHODS
Knee joints of anesthetized rats were perfused with BK (0.1-1.0 microM), and synovial plasma extravasation (PE) was evaluated by spectrophotometrical measurement of Evans Blue leakage. To examine the signaling pathway, B1 antagonist [des-Arg10]-HOE140 (0.1-1.0 microM) and B2 antagonist HOE140 (0.05-1.0 microM), calcitonin gene-related peptide (CGRP) antagonist CGRP8-37 (0.5-1.0 microM), prostaglandin E2 antagonist AH-6809 (0.1-1.0 microM), and histamine H1 antagonist mepyramine (0.1-1.0 microM) were used. Nociceptin (0.0001-1.0 microM) and antagonist J-113397 were tested for modulation of BK-induced PE. The analyses were compared side-by-side with 5-hydroxytryptamine-induced PE.


RESULTS
BK perfusion dose-dependently induced PE, which was blocked by HOE140, CGRP8-37, AH-6809, and mepyramine. It was also inhibited by nociceptin, which could be reversed by antagonist J-113397. In contrast, 5-hydroxytryptamine-induced PE was biphasically regulated by nociceptin and was not antagonized by CGRP8-37.


CONCLUSIONS
BK-induced PE is mediated by B2 receptors and may involve CGRP, prostaglandin, and histamine pathways. BK-induced PE is inhibited by nociceptin through the activation of ORL1 receptors. There are differences between BK- and 5-hydroxytryptamine-induced inflammation in signaling and modulation.
Moriyama
Kumi
K
Department of Anesthesia and Perioperative Care, University of California, San Francisco, 94143, USA. moriyama@ks.kyorin-u.ac.jp
Liu
Jia
J
Jang
Yeon
Y
Chae
Yun Jeong
YJ
Wang
Yan
Y
Mitchell
James
J
Grond
Stefan
S
Han
Xiaokang
X
Xing
Yilei
Y
Xie
Guo-xi
GX
Pierce Palmer
Pamela
P
D000818:Animals; D001920:Bradykinin / Q000378:metabolism*; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D004396:Coloring Agents / Q000378:metabolism; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000378:metabolism; D005070:Evans Blue / Q000378:metabolism; D006632:Histamine / Q000378:metabolism; D006801:Humans; D007719:Knee Joint / Q000378:metabolism*; D008297:Male; D018847:Opioid Peptides / Q000378:metabolism*; D010949:Plasma / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D043783:Receptor, Bradykinin B1 / Q000378:metabolism*; D043782:Receptor, Bradykinin B2 / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000097629:Nociceptin
D001920:Bradykinin; D065169:Bradykinin B1 Receptor Antagonists; D065094:Bradykinin B2 Receptor Antagonists; D015740:Calcitonin Gene-Related Peptide; D004396:Coloring Agents; D015232:Dinoprostone; D005070:Evans Blue; D006632:Histamine; D018847:Opioid Peptides; D043783:Receptor, Bradykinin B1; D043782:Receptor, Bradykinin B2; D012701:Serotonin; D000097629:Nociceptin