Figure 5. 2-Arachidonoylglycerol, 1-arachidonoylglycerol and the stable 2-arachidonoylglycerol analog noladin ether activate native TRPV1.

(A) Concentration-response curves for 2-arachidonoylglycerol (2-AG), 1-arachidonoylglycerol (1-AG) and noladin ether (NE) in the presence and absence of the TRPV1 antagonist capsazepine. Control experiments were performed in the presence of vehicle (0.1% ethanol). The MAGL inhibitor methylarachidonylfluorophosphonate (30 nM) was present in all experiments with 2-AG and 1-AG. The area under the curve was smaller in the presence than in the absence of capsazepine for all three lipids (P<0.01). Data are expressed as mean ± s.e.m. (n = 5–8).Vasodilator effect of 10 µM 2-AG (B) and NE (C) in isolated mesenteric arterial segments from TRPV1 knock-out (TRPV1^−/−) and wild-type (TRPV1^+/+) mice (n = 5). While 2-AG and NE produced only small responses in TRPV1^−/− mice, subsequent application of the TRPA1 activator Δ⁹-tetrahydrocannabinol (THC) elicited an almost complete vasorelaxation, amounting to 90±2.5% and 94±2.0%, respectively (traces). The dashed lines show the basal tension level before addition of phenylephrine (PhE). Data are expressed as mean ± s.e.m.. *P<0.05, **P<0.01.