Gervasi María Gracia, Rapanelli Maximiliano, Ribeiro María Laura, Farina Mariana, Billi Silvia, Franchi Ana María, Perez Martinez Silvina
Facultad de Medicina, Centro de Estudios Farmacológicos y Botánicos, Universidad de Buenos Aires, Buenos Aires, Argentina.
Reproduction. 2009 Mar;137(3):403-14. doi: 10.1530/REP-08-0204. Epub 2008 Nov 28.
Anandamide binds to cannabinoid receptors and plays several central and peripheral functions. The aim of this work was to study the possible role for this endocannabinoid in controlling sperm-oviduct interaction in mammals. We observed that bull sperm and bovine oviductal epithelial cells express cannabinoid receptors, CB1 and CB2, and fatty acid amide hydrolase, the enzyme that controls intracellular anandamide levels. A quantitative assay to determine whether anandamide was involved in bovine sperm-oviduct interaction was developed. R(+)-methanandamide, a non-hydrolysable anandamide analog, inhibited sperm binding to and induced sperm release from oviductal epithelia. Selective CB1 antagonists (SR141716A or AM251) completely blocked R(+)-methanandamide effects. However, SR144528, a selective CB2 antagonist, did not exert any effect, indicating that only CB1 was involved in R(+)-methanandamide effect. This effect was not caused by inhibition of the sperm progressive motility or by induction of the acrosome reaction. Overall, our findings indicate for the first time that the endocannabinoid system is present in bovine sperm and oviductal epithelium and that anandamide modulates the sperm-oviduct interaction, by inhibition of sperm binding and induction of sperm release from oviductal epithelial cells, probably by activating CB1 receptors.
花生四烯乙醇胺与大麻素受体结合并发挥多种中枢和外周功能。这项工作的目的是研究这种内源性大麻素在控制哺乳动物精子-输卵管相互作用中可能发挥的作用。我们观察到公牛精子和牛输卵管上皮细胞表达大麻素受体CB1和CB2以及脂肪酸酰胺水解酶,该酶可控制细胞内花生四烯乙醇胺的水平。我们开发了一种定量测定方法来确定花生四烯乙醇胺是否参与牛精子-输卵管相互作用。R(+)-甲烷基花生四烯酸乙醇胺,一种不可水解的花生四烯乙醇胺类似物,抑制精子与输卵管上皮的结合并诱导精子从输卵管上皮释放。选择性CB1拮抗剂(SR141716A或AM251)完全阻断了R(+)-甲烷基花生四烯酸乙醇胺的作用。然而,选择性CB2拮抗剂SR144528没有产生任何作用,表明只有CB1参与了R(+)-甲烷基花生四烯酸乙醇胺的作用。这种作用不是由抑制精子的前进运动或诱导顶体反应引起的。总体而言,我们的研究结果首次表明内源性大麻素系统存在于牛精子和输卵管上皮中,并且花生四烯乙醇胺可能通过激活CB1受体来调节精子-输卵管相互作用,即抑制精子结合并诱导精子从输卵管上皮细胞释放。