Inhibition of exocytotic noradrenaline release by presynaptic cannabinoid CB1 receptors on peripheral sympathetic nerves
Inhibition of exocytotic noradrenaline release by presynaptic cannabinoid CB1 receptors on peripheral sympathetic nerves
复制标题
DOI：
10.1111/j.1476-5381.1996.tb15639.x
复制
发表时间：
1996-08-01
影响因子：
7.3
通讯作者：
Kunos, G
中科院分区：
文献类型：
--
作者：
Ishac, EJN;Jiang, L;Kunos, G
1植物大麻素或内源性配体大麻素激活CB 1受体，通过麻醉大鼠的交感神经抑制作用引起低血压。在小鼠离体输精管中，CB 1受体的激活抑制电诱发的抽搐反应。为了确定这些效应是否与突触前抑制去甲肾上腺素（NA）释放有关，我们检查了Delta（9）-四氢大麻酚（Delta（9）-THC）、大麻素和CB 1拮抗剂SR 141716 A对大鼠离体心房和输精管中胞吐NA释放的影响。2在预载[H-3]-NA的离体心房和输精管中，电场刺激引起[H-3]-NA的释放，该释放被0.5 μ M的河豚毒素消除，并被0.3-10 μ M的Δ（9）-THC或花生四烯酸浓度依赖性地抑制。SR 141716 A（1-10 μ M）可竞争性拮抗Delta（9）-THC和花生四烯酸的抑制作用。3酪胺（1 μ M）也可诱导[H-3]-NA释放，而心房或输精管中的[H-3]-NA释放不受河豚毒素、Delta（9）-THC或花生四烯酸的影响。4 CB 1受体mRNA存在于上级颈神经节以及全脑、小脑、下丘脑、逆转录-聚合酶链反应显示，脾脏和输精管中有表达，延髓和心房中无表达。没有证据表明CB 1A受体mRNA存在于神经节，大脑或小脑。这些结果表明，位于外周交感神经末梢的突触前CB 1受体的激活介导的交感神经抑制作用在体外和体内。
1 Activation of CB1 receptors by plant cannabinoids or the endogenous ligand, anandamide, causes hypotension via a sympathoinhibitory action in anaesthetized rats. In mouse isolated vas deferens, activation of CB1 receptors inhibits the electrically evoked twitch response. To determine if these effects are related to presynaptic inhibition of noradrenaline (NA) release, we examined the effects of Delta(9)-tetrahydrocannabinol (Delta(9)-THC), anandamide and the CB1 antagonist, SR141716A, on exocytotic NA release in rat isolated atria and vasa deferentia.2 In isolated atria and vasa deferentia preloaded with [H-3]-NA, electrical field stimulation caused [H-3]-NA release, which was abolished by tetrodotoxin 0.5 mu M and concentration-dependently inhibited by Delta(9)-THC or anandamide, 0.3-10 mu M. The inhibitory effect of Delta(9)-THC and anandamide was competitively antagonized by SR141716A, 1-10 mu M.3 Tyramine, 1 mu M, also induced [H-3]-NA release, which was unaffected by tetrodotoxin, Delta(9)-THC or anandamide in either atria or vasa deferentia.4 CB1 receptor mRNA is present in the superior cervical ganglion, as well as in whole brain, cerebellum, hypothalamus, spleen, and vas deferens and absent in medulla oblongata and atria, as demonstrated by reverse transcription-polymerase chain reaction. There was no evidence of the presence of CB1A receptor mRNA in ganglia, brain, or cerebellum. These results suggest that activation of presynaptic CB1 receptors located on peripheral sympathetic nerve terminals mediate sympathoinhibitory effects in vitro and in vivo.