Sibaev Andrei, Yuece Birol, Allescher Hans Dieter, Saur Dieter, Storr Martin, Kurjak Manfred
Department of Internal Medicine II, Ludwig-Maximilians-University Munich, Munich, Germany; Walter Brendel Zentrum, Ludwig-Maximilians-University Munich, Munich, Germany.
Department of Internal Medicine II, Ludwig-Maximilians-University Munich, Munich, Germany; Walter Brendel Zentrum, Ludwig-Maximilians-University Munich, Munich, Germany.
Pharmacol Rep. 2014 Apr;66(2):256-63. doi: 10.1016/j.pharep.2013.09.008. Epub 2014 Mar 3.
Endocannabinoids (EC) and the cannabinoid-1 (CB1) receptor are involved in the regulation of motility in the gastrointestinal (GI) tract. However, the underlying physiological mechanisms are not completely resolved. The purpose of this work was to study the physiological influence of the endocannabinoid anandamide, the putative endogenous CB1 active cannabinoid, and of the CB1 receptor on ascending peristaltic activity and to identify the involved neuro-neuronal, neuro-muscular and electrophysiological mechanisms.
The effects of anandamide and the CB1 receptor antagonist SR141716A were investigated on contractions of the circular smooth muscle of rat ileum and in longitudinal rat ileum segments where the ascending myenteric part of the peristaltic reflex was studied in a newly designed organ bath. Additionally intracellular recordings were performed in ileum and colon.
Anandamide significantly reduced cholinergic twitch contractions of ileum smooth muscle whereas SR141716A caused an increase. Anandamide reduced the ascending peristaltic contraction by affecting neuro-neuronal and neuro-muscular neurotransmission. SR141716A showed opposite effects and all anandamide effects were antagonized by SR141716A (1 μM). Anandamide reduced excitatory junction potentials (EJP) and inhibitory junction potentials (IJP), whereas intestinal slow waves were not affected.
CB1 receptors regulate force and timing of the intestinal peristaltic reflex and these actions involve interneurons and motor-neurons. The endogenous cannabinoid anandamide mediates these effects by activation of CB1 receptors. The endogenous cannabinoid system is permanently active, suggesting the CB1 receptor being a possible target for the treatment of motility related disorders.
内源性大麻素（EC）和大麻素-1（CB1）受体参与胃肠道（GI）动力的调节。然而，其潜在的生理机制尚未完全阐明。本研究旨在探讨内源性大麻素花生四烯乙醇胺（一种假定的内源性CB1活性大麻素）和CB1受体对升结肠蠕动活动的生理影响，并确定其中涉及的神经-神经元、神经-肌肉和电生理机制。
在新设计的器官浴槽中，研究了花生四烯乙醇胺和CB1受体拮抗剂SR141716A对大鼠回肠环形平滑肌收缩以及大鼠回肠纵行肌段（其中研究了蠕动反射的升结肠肌间部分）的影响。此外，还在回肠和结肠进行了细胞内记录。
花生四烯乙醇胺显著降低回肠平滑肌的胆碱能抽搐收缩，而SR141716A则使其增加。花生四烯乙醇胺通过影响神经-神经元和神经-肌肉神经传递来减少升结肠蠕动收缩。SR141716A表现出相反的作用，且1μM的SR141716A可拮抗花生四烯乙醇胺的所有作用。花生四烯乙醇胺降低兴奋性接头电位（EJP）和抑制性接头电位（IJP），而肠慢波不受影响。
CB1受体调节肠道蠕动反射的力量和时间，这些作用涉及中间神经元和运动神经元。内源性大麻素花生四烯乙醇胺通过激活CB1受体介导这些效应。内源性大麻素系统持续活跃，提示CB1受体可能是治疗动力相关疾病的靶点。
