Junichi Kurihara1,*, Michiru Nishigaki1, Shigeto Suzuki1, Yoko Okubo1, Yoshinobu Takata1, Shinji Nakane2, Takayuki Sugiura2, Keizo Waku2 and Hitoshi Kato1
1Department of Pharmacology and 2Department of Hygienic Chemistry and Nutrition, Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa 199-0195, Japa
*Corresponding author. FAX: +81-426-85-3726, E-mail: jun-kuri@pharm.teikyo-u.ac.jp
Abstract: Anandamide (10-7 and 10-6 M) as well as a synthetic cannabinoid HU210 (10-8 to 10-6 M) suppressed the norepinephrine release evoked by perivascular nerve stimulation (PNS) of the rat heart Langendorff's preparation. The effects of HU210 and the lower dose of anandamide were completely blocked by the cannabinoid CB1-receptor antagonist AM251, while that of anandamide at 10-6 M was partly mediated by arachidonate-derived metabolites. 2-Arachidonoylglycerol (2-AG), at 10-6 M in the presence of DFP and indomethacin, increased PNS-evoked norepinephrine release, which was completely blocked by AM251. The present results suggest that the two endocannabinoids may oppositely participate in the CB1-receptor-mediated modulation of sympathetic norepinephrine release.
Keywords: 2-Arachidonoylglycerol, Anandamide, Norepinephrine release
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