Pertwee R, Griffin G, Hanus L, Mechoulam R
Department of Biomedical Sciences, Marischal College, University of Aberdeen, Scotland, UK.
Eur J Pharmacol. 1994 Jul 1;259(2):115-20. doi: 10.1016/0014-2999(94)90499-5.
Anandamide (20:3, n - 6) (homo-gamma-linolenylethanolamide) and anandamide (22:4, n - 6) (7,10,13,16-docosatetraenylethanolamide) are known to be present in porcine brain and to undergo specific binding to cannabinoid binding sites. We have now shown that both compounds inhibit the electrically evoked twitch response of the mouse isolated vas deferens (IC50 = 99.3 and 95.5 nM respectively) indicating that they also have the ability to elicit a response. As electrically evoked contractions of the mouse vas deferens are also inhibited by the endogenous cannabinoid, anandamide (20:4, n - 6) (arachidonylethanolamide; IC50 = 52.7 nM), and by other cannabinoids, we conclude that anandamide (20:3, n - 6) and (22:4, n - 6), may, together with anandamide (20:4, n - 6), serve as endogenous cannabinoid receptor agonists. This conclusion is supported by our other main finding, that vasa deferentia show tolerance to the inhibitory effects of anandamide (20:3, n - 6) and anandamide (22:4, n - 6) when obtained from mice subjected to a delta 9-tetrahydrocannabinol pretreatment that is known to induce cannabinoid tolerance.
花生四烯乙醇胺（20:3，n - 6）（同型γ-亚麻酸乙醇酰胺）和花生四烯乙醇胺（22:4，n - 6）（7,10,13,16-二十二碳四烯乙醇酰胺）已知存在于猪脑中，并能与大麻素结合位点发生特异性结合。我们现已表明，这两种化合物均能抑制小鼠离体输精管的电诱发抽搐反应（IC50分别为99.3和95.5 nM），这表明它们也具有引发反应的能力。由于小鼠输精管的电诱发收缩也受到内源性大麻素花生四烯乙醇胺（20:4，n - 6）（花生四烯酸乙醇酰胺；IC50 = 52.7 nM）以及其他大麻素的抑制，我们得出结论，花生四烯乙醇胺（20:3，n - 6）和（22:4，n - 6）可能与花生四烯乙醇胺（20:4，n - 6）一起作为内源性大麻素受体激动剂。我们的另一项主要发现支持了这一结论，即当从接受已知可诱导大麻素耐受性的Δ9-四氢大麻酚预处理的小鼠获得输精管时，输精管对花生四烯乙醇胺（20:3，n - 6）和花生四烯乙醇胺（22:4，n - 6）的抑制作用表现出耐受性。
