The long-term exposure of rat cultured dorsal root ganglion cells to bradykinin induced the release of prostaglandin E2 by the activation of cyclooxygenase-2.
The effects of long-term exposure of primary cultured rat dorsal root ganglion (DRG) cells to bradykinin (BK), compared to short-term exposure, were investigated to establish whether BK could induce prostaglandin E2 (PGE2) release from DRG cells. Short-term exposure (30 min) resulted in a small but significant amount of PGE2 release which was mainly inhibited by a selective COX-1 inhibitor, SC-560 but only partially by a selective COX-2 inhibitor, NS-398, and did not induce COX-2 protein as determined by Western blotting. In contrast, long-term exposure (3 h) induced a large amount of PGE2 release, which was completely abolished by indomethacin or NS-398. The level of COX-2 mRNA began to be detected by ribonuclease protection assay after 30 min of 100 nM BK exposure, maintained maximal expression for 1 h, and subsequently declined to the basal level. The level of COX-2 protein was expressed to follow the time course of COX-2 mRNA induction by BK in a delayed but similar kinetic manner. The expression of COX-2 induced by BK in DRG cells was inhibited by a BK B2 receptor antagonist, HOE140, but not a B1 receptor antagonist, Lys-des-Arg9, (Leu8)-BK. Thus, BK has been shown to induce COX-2 protein by B2 receptor, which may cause prostanoid generation in rat DRG cells, which may play an important role in the pathogenesis of inflammatory pain and hyperalgesia around the primary sensory neurons.
Department of Pharmacology, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan. ainoue@hiroshima-u.ac.jp
Atsuko
A
Inoue
Mikiko
M
Iwasa
Yumi
Y
Nishikura
Shinya
S
Ogawa
Ayaka
A
Nakasuka
Yoshihiro
Y
Nakata
D000818:Animals; D001345:Autoradiography / Q000379:methods; D015153:Blotting, Western / Q000379:methods; D001920:Bradykinin / Q000494:pharmacology*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D001920:Bradykinin