Receptor mediation and nociceptin inhibition of bradykinin-induced plasma extravasation in the knee joint of the rat.

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Moriyama K, Liu J, Jang Y, Chae YJ, Wang Y, Mitchell J, Grond S, Han X, Xing Y, Xie GX, Pierce Palmer P

Receptor mediation and nociceptin inhibition of bradykinin-induced plasma extravasation in the knee joint of the rat.

Inflamm Res. 2009 Dec;58(12):873-80. doi: 10.1007/s00011-009-0058-y. Epub 2009 Jun 21.

PubMed ID

19544046 [ View in PubMed

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Abstract

OBJECTIVE AND DESIGN: The aim was to investigate the signaling mechanisms and regulation of bradykinin (BK)-induced inflammation in rat knee joint. MATERIALS AND 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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Mepyramine	Histamine H1 receptor	Protein	Humans	Yes	Antagonist	Details