Differential effects of anandamide on acetylcholine release in the guinea‐pig ileum mediated via vanilloid and non‐CB1 cannabinoid receptors
Differential effects of anandamide on acetylcholine release in the guinea‐pig ileum mediated via vanilloid and non‐CB1 cannabinoid receptors
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DOI：
10.1038/sj.bjp.0704220
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发表时间：
2001-09
影响因子：
7.3
通讯作者：
C. Mang;D. Erbelding;H. Kilbinger
中科院分区：
文献类型：
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作者：
C. Mang;D. Erbelding;H. Kilbinger
在[3H] -胆碱预孵育豚鼠回肠肌丛-纵肌制备过程中，研究了阿南德胺对[3H] -乙酰胆碱释放和肌肉收缩的影响。Anandamide增加了基础[3H]‐乙酰胆碱释放（pEC506.3）和肌肉张力（pEC506.3）。1 μMcapsazepine （pKB7.5和7.6）和拮抗剂CP99994 + SR142801联合阻断nk1和NK3tachykinin受体（各0.1 μM）使anandamide的浓度响应曲线右移。cb1和cb2受体拮抗剂SR141716A （1 μM）和SR144528 （30 nM）没有改变anandamide的促进作用。Anandamide抑制电诱发的[3H]乙酰胆碱释放（pEC505.8）和收缩（pEC505.2）。10 μManandamide对毒蕈碱激动剂甲胆碱的收缩反应无显著影响。capsazepine （1 μM）、SR144528 （30 nM）、CP99994 + SR142801（各0.1 μM）对anandamide的抑制作用均无显著影响。SR141716A （1 μM）使anandamide的抑制浓度-响应曲线向右移动，产生pkb值为6.6和6.2。CP55940抑制了诱发的[3H] -乙酰胆碱的释放和收缩，SR141716A （0.1 μM）使CP55940的浓度-响应曲线右移，pkb值分别为8.4和8.9。实验证实胆碱能肌神经细胞上存在抑制释放的cb1受体。我们得出结论，anandamide通过刺激一种不同于cb1和cb2受体的受体来抑制乙酰胆碱的释放。此外，anandamide通过刺激位于初级传入纤维的香草样受体增加基础乙酰胆碱释放。英国药理学杂志（2001）134,161-167；doi: 10.1038 / sj.bjp.0704220
The effects of anandamide on [3H]‐acetylcholine release and muscle contraction were studied on the myenteric plexus‐longitudinal muscle preparation of the guinea‐pig ileum preincubated with [3H]‐choline.Anandamide increased both basal [3H]‐acetylcholine release (pEC506.3) and muscle tone (pEC506.3). The concentration‐response curves for anandamide were shifted to the right by 1 μMcapsazepine (pKB7.5 and 7.6), and by the combined blockade of NK1and NK3tachykinin receptors with the antagonists CP99994 plus SR142801 (each 0.1 μM). The CB1and CB2receptor antagonists, SR141716A (1 μM) and SR144528 (30 nM), did not modify the facilitatory effects of anandamide.Anandamide inhibited the electrically‐evoked release of [3H]‐acetylcholine (pEC505.8) and contractions (pEC505.2). The contractile response to the muscarinic agonist methacholine was not significantly affected by 10 μManandamide.The inhibitory effects of anandamide were not changed by either capsazepine (1 μM), SR144528 (30 nM) or CP99994 plus SR142801 (each 0.1 μM). SR141716A (1 μM) produced rightward shifts in the inhibitory concentration‐response curves for anandamide yielding pKBvalues of 6.6 and 6.2.CP55940 inhibited the evoked [3H]‐acetylcholine release and contractions, and SR141716A (0.1 μM) shifted the concentration‐response curves of CP55940 to the right with pKBvalues of 8.4 and 8.9.The experiments confirm the existence of release‐inhibitory CB1receptors on cholinergic myenteric neurones. We conclude that anandamide inhibits the evoked acetylcholine releaseviastimulation of a receptor that is different from the CB1and CB2receptor. Furthermore, anandamide increases basal acetylcholine releaseviastimulation of vanilloid receptors located at primary afferent fibres.British Journal of Pharmacology(2001)134, 161–167; doi:10.1038/sj.bjp.0704220