title: CB(1) cannabinoid receptor stimulation modulates transient receptor potential vanilloid receptor 1 activities in calcium influx and substance P Release in cultured rat dorsal root ganglion cells.
abstract: Cannabinoids have been reported to have analgesic properties in animals of acute nociception or of inflammatory and neuropathic pain models, but the mechanisms by which they exert such alleviative effects are not yet fully understood. We investigated whether the CB(1)-cannabinoid-receptor agonist HU210 modulates the capsaicin-induced (45)Ca(2+) influx and substance P like-immunoreactivity (SPLI) release in cultured rat dorsal root ganglion (DRG) cells. HU210 attenuated the capsaicin-induced (45)Ca(2+) influx and this effect was reversed by the CB(1) antagonist AM251. Treatment of DRG cells with 100 nM bradykinin for 3 h potentiated capsaicin-induced SPLI release accompanied with the induction of cyclooxygenase-2 mRNA expression. The potentiation of SPLI release by bradykinin was reversed by HU210 or the protein kinase A (PKA) inhibitor H-89. HU210 also reduced forskolin-induced cyclic AMP production and forskolin-induced potentiation of SPLI release. These results suggest that CB(1) could inhibit either the capsaicin-induced Ca(2+) influx or the potentiation of capsaicin-induced SPLI release by a long-term treatment with bradykinin through involvement of a cyclic-AMP-dependent PKA pathway. In conclusion, CB(1)-receptor stimulation modulates the activities of transient receptor potential vanilloid receptor 1 in cultured rat DRG cells.
authors.affiliation: Department of Anesthesiology and Critical Care, Division of Clinical Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima. oshitak@hiroshima-u.ac.jp
authors.forename: Kyoko
authors.initials: K
authors.lastname: Oshita
authors.forename: Atsuko
authors.initials: A
authors.lastname: Inoue
authors.forename: He-Bin
authors.initials: HB
authors.lastname: Tang
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nakata
authors.forename: Masashi
authors.initials: M
authors.lastname: Kawamoto
authors.forename: Osafumi
authors.initials: O
authors.lastname: Yuge
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002211:Capsaicin / Q000494:pharmacology; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000031:analogs & derivatives / Q000494:pharmacology; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D010880:Piperidines / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D043882:Receptors, Cannabinoid / Q000378:metabolism*; D011955:Receptors, Drug / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
chemical_list: D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D004791:Enzyme Inhibitors; D007546:Isoquinolines; D010880:Piperidines; D011720:Pyrazoles; D012333:RNA, Messenger; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013449:Sulfonamides; D013373:Substance P; C103505:AM 251; D013759:Dronabinol; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; C062018:HU 211; D002211:Capsaicin; D001920:Bradykinin; D002118:Calcium