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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >Presynaptic effects of anandamide and WIN55,212-2 on glutamatergic nerve endings isolated from rat hippocampus.
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Presynaptic effects of anandamide and WIN55,212-2 on glutamatergic nerve endings isolated from rat hippocampus.

机译：Anandamide和WIN55,212-2对大鼠海马分离出的谷氨酸能神经末梢的突触前作用。

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摘要

We examined the effects of the endocannabinoide-anandamide (AEA), the synthetic cannabinoid, WIN55,212-2, and the active phorbol ester, 4-beta-phorbol 12-myristate 13-acetate (4-beta-PMA), on the release of [(3)H]d-Aspartate ([(3)H]d-ASP) from rat hippocampal synaptosomes. Release was evoked with three different stimuli: (1) KCl-induced membrane depolarization, which activates voltage-dependent Ca(2+) channels and causes limited neurotransmitter exocytosis, presumably from ready-releasable vesicles docked in the active zone; (2) exposure to the Ca(2+) ionophore-A23187, which causes more extensive transmitter release, presumably from intracellular reserve vesicles; and (3) K(+) channel blockade by 4-aminopyridine (4-AP), which generates repetitive depolarization that stimulates release from both ready-releasable and reserve vesicles. AEA produced concentration-dependent inhibition of [(3)H]d-ASP release stimulated with 15 mM KCl (E(max)=47.4+/-2.8; EC(50)=0.8 microM) but potentiated the release induced by 4-AP (1mM) (+22.0+/-1.3% at 1 microM) and by A23187 (1 microM) (+98.0+/-5.9% at 1 microM). AEA's enhancement of the [(3)H]d-ASP release induced by the Ca(2+) ionophore was mimicked by 4-beta-PMA, which is known to activate protein kinase C (PKC), and the increases produced by both compounds were completely reversed by synaptosome treatment with staurosporine (1 microM), a potent PKC blocker. In contrast, WIN55,212-2 inhibited the release of [(3)H]d-ASP evoked by KCl (E(max)=47.1+/-2.8; EC(50)=0.9 microM) and that produced by 4-AP (-26.0+/-1.5% at 1 microM) and had no significant effect of the release induced by Ca(2+) ionophore treatment. AEA thus appears to exert a dual effect on hippocampal glutamatergic nerve terminals. It inhibits release from ready-releasable vesicles and potentiates the release observed during high-frequency stimulation, which also involves the reserve vesicles. The latter effect is mediated by PKC. These findings reveal novel effects of AEA on glutamatergic nerve terminals and demonstrate that the effects of endogenous and synthetic cannabinoids are not always identical.
机译：我们检查了内源性大麻素（AEA），合成大麻素WIN55,212-2和活性佛波醇酯4-β-佛波醇12-肉豆蔻酸酯13-乙酸酯（4-β-PMA）的作用。从大鼠海马突触小体释放[（3）H] d-天冬氨酸（[（3）H] d-ASP）。释放是由三种不同的刺激引起的：（1）KCl诱导的膜去极化，这激活了电压依赖性Ca（2+）通道并引起有限的神经递质胞吐作用，推测是来自停泊在活动区的易释放囊泡; （2）暴露于Ca（2+）离子载体A23187，这可能导致更广泛的递质释放，大概是从细胞内储备小泡释放出来的; （3）4-氨基吡啶（4-AP）阻滞K（+）通道，产生重复的去极化作用，从而刺激可释放和备用囊泡的释放。 AEA对15 mM KCl（E（max）= 47.4 +/- 2.8; EC（50）= 0.8 microM）刺激的[（3）H] d-ASP释放产生浓度依赖性抑制，但增强了4- AP（1mM）（在1 microM时为+22.0 +/- 1.3％）和A23187（1 microM）（在1 microM时为+98.0 +/- 5.9％）。 AEA对由Ca（2+）离子载体诱导的[（3）H] d-ASP释放的增强被4-beta-PMA模仿，后者可激活蛋白激酶C（PKC），并且两者均会增加通过用强效PKC阻滞剂staurosporine（1 microM）进行突触体处理，可以完全逆转这些化合物。相反，WIN55,212-2抑制了KCl引起的[（3）H] d-ASP的释放（E（max）= 47.1 +/- 2.8; EC（50）= 0.9 microM）以及由4- AP（-1 microM时为-26.0 +/- 1.5％），对Ca（2+）离子载体处理诱导的释放没有明显影响。因此，AEA似乎对海马谷氨酸能神经末梢产生双重作用。它抑制了易于释放的囊泡的释放，并增强了高频刺激过程中观察到的释放，高频刺激也涉及储备囊泡。后者的作用是由PKC介导的。这些发现揭示了AEA对谷氨酸能神经末梢的新作用，并证明内源性和合成大麻素的作用并不总是相同的。

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