Reduction of the fertilizing capacity of sea urchin sperm by cannabinoids derived from marihuana. III. Activation of phospholipase A2 in sperm homogenate by delta 9-tetrahydrocannabinol.
Reduction of the fertilizing capacity of sea urchin sperm by cannabinoids derived from marihuana. III. Activation of phospholipase A2 in sperm homogenate by delta 9-tetrahydrocannabinol.
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大麻中提取的大麻素会降低海胆精子的受精能力。
DOI：
10.1016/0006-2952(91)90051-6
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发表时间：
1991
影响因子：
5.8
通讯作者：
Schuel,H
中科院分区：
文献类型：
--
作者：
Chang,MC;Berkery,D;Laychock,SG;Schuel,H
Δ9-四氢大麻酚（THC）对卵冻诱导的顶体反应的抑制与海胆精子中核膜的局部破坏和脂质沉积的形成有关。这表明THC可以激活精子内的磷脂酶。我们现在报告的影响THC对磷脂酶A2活性的海胆精子匀浆使用1-硬脂酰2-[1- 14 C]花生四烯酸磷脂酰胆碱为底物。在与酶孵育30分钟后测量放射性花生四烯酸的释放。在无外源Ca ~（2+）存在下，100 μ MTHC使磷脂酶A_2活性显著升高（P < 0.001）。THC对磷脂酶A2的激活具有浓度（1-100 μM）和时间（0-30 min）依赖性。外源性钙（10 mM）显著增强基础（P < 0.001）和THC刺激（P < 0.005）的磷脂酶A2活性。钙离子螯合剂[乙二醇双（β-氨基乙基醚）N，N，N′，N′-四乙酸（EGTA）和1，2-双（O-氨基苯氧基）乙烷-N，N，N′，N′-四乙酸（BAPTA）]可抑制精子匀浆中磷脂酶A2的基础水平，并阻止THC对磷脂酶A2的激活。亚微摩尔水平的游离钙离子需要THC刺激磷脂酶A2。大麻酚模拟THC对顶体反应的影响，也激活精子匀浆中的磷脂酶A2。这些结果表明，THC可能通过激活钙依赖性磷脂酶A2来改变精子中的脂质代谢。来自这一过程的推定代谢产物可能会抑制顶体反应，从而降低海胆精子的受精能力。
Inhibition of the egg jelly induced acrosome reaction by Δ9-tetrahydrocannabinol (THC) is associated with the localized disruption of the nuclear envelope and the formation of lipid deposits in sea urchin sperm. This suggests that THC may activate phospholipase(s) within the sperm. We now report effects of THC on phospholipase A2activity in homogenates of sea urchin sperm using 1-stearoyl2-[1-14C] arachidonyl phosphatidylcholine as substrate. The release of radioactive arachidonic acid was measured after a 30-min incubation with the enzyme. In the absence of exogenous Ca2+, 100 μM THC produced a significant (P < 0.001) increase in phospholipase A2activity. THC activated phospholipase A2in a concentration (1–100 μM) and time-dependent (0–30 min) manner. Exogenous calcium (10 mM) significantly augmented basal (P < 0.001) and THC-stimulated (P < 0.005) phospholipase A2activity. Calcium chelators [ethylene glycol bis(β-aminoethyl ether)N,N,N′,N′,-tetraacetic acid (EGTA) and 1,2-bis(O-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA)] inhibited the basal level of phospholipase A2activity in the sperm homogenate, and prevented the activation of phospholipase A2by THC. Submicromolar levels of free calcium ions were required for THC stimulation of phospholipase A2. Cannabinol which mimics the effects of THC on the acrosome reaction also activated phospholipase A2in sperm homogenate. These results suggest that THC may alter lipid metabolism in sperm by activating calcium-dependent phospholipase A2. Putative metabolites derived from this process may inhibit the acrosome reaction and thereby reduce the fertilizing capacity of sea urchin sperm.