title: NSAID zaltoprofen possesses novel anti-nociceptive mechanism through blockage of B2-type bradykinin receptor in nerve endings.
abstract: Zaltoprofen, a propionic acid derivative of non-steroidal anti-inflammatory drugs (NSAIDs), was shown to have more powerful inhibitory effects to bradykinin (BK)-nociception than other NSAIDs. However, the molecular mechanisms underlying this potent analgesia are not yet fully understood. Here we attempted to clarify the molecular mechanism underlying zaltoprofen-induced analgesia on BK-induced nociception by a novel algogenic-induced paw flexion (APF) test in mice. The intraplantar (i.pl.) injection of zaltoprofen at 1nmol showed strong analgesic action on BK (i.pl.)-induced nociceptive flexor responses, whereas loxoprofen or its active metabolite loxoprofen-SRS did not. Zaltoprofen also inhibited the nociception induced by [Tyr8]-BK, a specific agonist of B2-type BK receptor, but did not affect the nociception by [Lys-des-Arg9]-BK, a specific agonist of B1-type BK receptor. However, zaltoprofen did not affect the substance P-induced nociception, which is mediated by common post-receptor signaling through nociceptive fibers with BK-ones. All these results suggest that NSAID zaltoprofen possesses novel anti-nociceptive mechanism, which inhibits B2-type BK receptor function in nerve endings.
authors.affiliation: Division of Molecular Pharmacology and Neuroscience, Nagasaki University Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan. dm05052b@stcc.nagasaki-u.ac.jp
authors.forename: Misaki
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D065094:Bradykinin B2 Receptor Antagonists; D008297:Male; D051379:Mice; D009411:Nerve Endings / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement; D011422:Propionates / Q000494:pharmacology* / Q000627:therapeutic use; D043782:Receptor, Bradykinin B2 / Q000819:agonists; D012584:Sciatic Nerve / Q000503:physiopathology; D013373:Substance P
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001578:Benzopyrans; D065094:Bradykinin B2 Receptor Antagonists; D011422:Propionates; D043782:Receptor, Bradykinin B2; C043940:pyranoprofen; D013373:Substance P