Cannabinoid CB1 receptor activation, pharmacological blockade, or genetic ablation affects the function of the muscarinic auto- and heteroreceptor

Cannabinoid CB1 receptor activation, pharmacological blockade, or genetic ablation affects the function of the muscarinic auto- and heteroreceptor
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大麻素 CB1 受体激活、药理学阻断或基因消除会影响毒蕈碱自身和异源受体的功能

DOI:
10.1007/s00210-011-0717-8
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发表时间:
2012
期刊:
Naunyn-Schmiedeberg's Archives of Pharmacology
影响因子:
--
通讯作者:
Schlicker E
Schlicker E
中科院分区:
--
文献类型:
--
作者:
Schulte K;Steingrüber N;Jergas B;Redmer A;Kurz CM;Buchalla R;Lutz B;Zimmer A;Schlicker E

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不同类型的突触前抑制性Gαi/o蛋白偶联受体通常不是彼此独立地起作用,而是受体X的预激活损害了通过受体Y介导的作用。然而,这种相互作用是否延伸到胆碱能神经元上的大麻素CB 1受体是未知的,因此我们研究了它的激活、药理学阻断或遗传失活是否影响其他突触前抑制性受体的功能。在用3 H-胆碱或3 H-去甲肾上腺素预孵育的灌流啮齿动物组织中测定电诱发的乙酰胆碱或去甲肾上腺素释放。Western blotting法检测海马突触体M 2受体、Gαi和Gα o蛋白的表达。LC-MS/MS法测定海马素和2-花生四烯酸甘油水平。胆碱受体激动剂oxotremorine对海马脑片乙酰胆碱释放的抑制作用通过遗传CB 1受体消融(小鼠)和CB 1拮抗剂利莫那班(大鼠但不是小鼠)增加,并通过大麻素受体激动剂(小鼠)减少。在小鼠组织中,CB 1受体消融还增加了δ阿片受体激动剂对海马中乙酰胆碱释放的影响,以及oxotremorine对输精管中去甲肾上腺素释放的影响。CB 1受体阻断在很小程度上增加了Gα蛋白水平,而不影响Gα 1和M2受体蛋白或海马中花生四烯酸和花生四烯酸甘油的水平。总之,CB 1受体与啮齿动物海马胆碱能神经元上的毒蕈碱受体和δ阿片受体以及小鼠输精管去甲肾上腺素能神经元上的毒蕈碱受体显示出抑制性相互作用。
Different types of presynaptic inhibitory Gαi/oprotein-coupled receptors usually do not act independently of each other but rather pre-activation of receptor X impairs the effect mediated via receptor Y. It is, however, unknown whether this interaction extends to the cannabinoid CB1receptor on cholinergic neurones and hence we studied whether its activation, pharmacological blockade, or genetic inactivation affects the function of other presynaptic inhibitory receptors. The electrically evoked acetylcholine or noradrenaline release was determined in superfused rodent tissues preincubated with3H-choline or3H-noradrenaline. The muscarinic M2receptor, Gαi, and Gαoproteins were determined in hippocampal synaptosomes by Western blotting. Hippocampal anandamide and 2-arachidonoyl glycerol levels were determined by LC-MS/MS. The inhibitory effect of the muscarinic receptor agonist oxotremorine on acetylcholine release in hippocampal slices was increased by genetic CB1receptor ablation (mouse) and the CB1antagonist rimonabant (rat but not mouse) and decreased by a cannabinoid receptor agonist (mouse). In mouse tissues, CB1receptor ablation also increased the effect of a δ opioid receptor agonist on acetylcholine release in the hippocampus and the effect of oxotremorine on noradrenaline release in the vas deferens. CB1receptor ablation, to a very slight extent, increased Gαoprotein levels without affecting either Gαiand M2receptor protein or the levels of anandamide and 2-arachidonoyl glycerol in the hippocampus. In conclusion, the CB1receptor shows an inhibitory interaction with the muscarinic and δ opioid receptor on cholinergic neurones in the rodent hippocampus and with the muscarinic receptor on noradrenergic neurones in the mouse vas deferens.
强啡肽 A (1-13)(一种内源性 κ-阿片受体激动剂)可逆转毒蕈碱自身受体激动剂引起的乙酰胆碱减少和学习障碍
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