Schuel H, Goldstein E, Mechoulam R, Zimmerman A M, Zimmerman S
Department of Anatomy and Cell Biology, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York 14214.
Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7678-82. doi: 10.1073/pnas.91.16.7678.
Anandamide (arachidonylethanolamide) is an endogenous cannabinoid receptor agonist in mammalian brain. Sea urchin sperm contain a high-affinity cannabinoid receptor similar to the cannabinoid receptor in mammalian brain. (-)-delta 9-Tetrahydrocannabinol (THC), the primary psychoactive cannabinoid in marihuana, reduces the fertilizing capacity of sea urchin sperm by blocking the acrosome reaction that normally is stimulated by a specific ligand in the egg's jelly coat. We now report that anandamide produces effects similar to those previously obtained with THC in Strongylocentrotus purpuratus in reducing sperm fertilizing capacity and inhibiting the egg jelly-stimulated acrosome reaction. Arachidonic acid does not inhibit the acrosome reaction under similar conditions. The adverse effects of anandamide on sperm fertilizing capacity and the acrosome reaction are reversible. The receptivity of unfertilized eggs to sperm and sperm motility are not impaired by anandamide. Under conditions where anandamide completely blocks the egg jelly-stimulated acrosome reaction, it does not inhibit the acrosome reaction artificially initiated by ionomycin, which promotes Ca2+ influx, and nigericin, which activates K+ channels in sperm. These findings provide additional evidence that the cannabinoid receptor in sperm plays a role in blocking the acrosome reaction, indicate that anandamide or a related molecule may be the natural ligand for the cannabinoid receptor in sea urchin sperm, and suggest that binding of anandamide to the cannabinoid receptor modulates stimulus-secretion-coupling in sperm by affecting an event prior to ion channel opening.
花生四烯酸乙醇胺(N-花生四烯酸乙醇胺)是哺乳动物大脑中的一种内源性大麻素受体激动剂。海胆精子含有一种与哺乳动物大脑中的大麻素受体相似的高亲和力大麻素受体。(-)-δ9-四氢大麻酚(THC)是大麻中的主要精神活性大麻素,它通过阻断通常由卵胶膜中的特定配体刺激的顶体反应来降低海胆精子的受精能力。我们现在报告,花生四烯酸乙醇胺在紫球海胆中产生的作用与之前用THC获得的作用相似,可降低精子受精能力并抑制卵胶刺激的顶体反应。在类似条件下,花生四烯酸不会抑制顶体反应。花生四烯酸乙醇胺对精子受精能力和顶体反应的不利影响是可逆的。未受精卵对精子的接受性和精子活力不受花生四烯酸乙醇胺的损害。在花生四烯酸乙醇胺完全阻断卵胶刺激的顶体反应的条件下,它不会抑制由离子霉素人工引发的顶体反应,离子霉素可促进Ca2+内流,尼日利亚菌素可激活精子中的K+通道。这些发现提供了额外的证据,表明精子中的大麻素受体在阻断顶体反应中起作用,表明花生四烯酸乙醇胺或相关分子可能是海胆精子中大麻素受体的天然配体,并表明花生四烯酸乙醇胺与大麻素受体的结合通过影响离子通道开放之前的事件来调节精子中的刺激-分泌偶联。