Department of Medical Pharmacology, Faculty of Medicine, Gazi University, Ankara, Turkey.
Department of Pharmacology, Gülhane Faculty of Pharmacy, University of Health Sciences, Ankara, Turkey.
Turk J Med Sci. 2022 Dec;52(6):1814-1820. doi: 10.55730/1300-0144.5527. Epub 2022 Dec 21.
Nicotine acts as an agonist of nicotinic acetylcholine receptors (nAChR). These receptors belong to a superfamily of ligand-gated ion channels. We previously demonstrated that nicotine increased electrical field stimulation (EFS)-induced contractile or relaxation responses, possibly by facilitating neurotransmitter release from nerve terminals in various rabbit tissues. Studies have shown that there is an interaction between the endocannabinoid and nicotinic systems. This study aimed to investigate the interaction between nicotine and the endocannabinoid system in the rabbit urine bladder and also investigate the enhancing effect of nicotine on EFS-induced contractile responses in rabbit isolated bladder smooth muscle and its interaction with the endocannabinoid system.
The New Zealand albino male adult rabbits were used for this study. Following scarification, the urine bladder was rapidly excised, and then uniform strips were prepared. Each strip was mounted under 1 g isometric resting tension in an organ bath containing 20 mL of Krebs-Henseleit solution. After obtaining EFS-induced contractile responses, 10-4 M concentrations of nicotine were applied to the preparations, and EFS was stopped after 5 stimulations. Following washing, the same experimental procedure was performed with the same tissue in the presence of AM251 (a cannabinoid CB1R antagonist, 10-6 M), AM630 (a cannabinoid CB2R antagonist, 10-6 M), and capsazepine (a vanilloid receptor antagonist, 3 × 10-6 M).
Nicotine enhanced the EFS-induced contraction responses by 17.16% ± 2.81% at a 4-Hz stimulation frequency. Cannabinoid receptor antagonists AM251 and AM630 reduced this increasing effect of nicotine although it was not significant and vanilloid receptor antagonist capsazepine did not significantly alter the nicotines' effect.
These results show that enhancing effect of nicotine in the smooth muscle of the rabbit bladder, even though it was not significant endocannabinoid system possibly have a role in nicotines' effect.
尼古丁作为烟碱型乙酰胆碱受体(nAChR)的激动剂。这些受体属于配体门控离子通道的超家族。我们之前的研究表明,尼古丁可增加电刺激(EFS)诱导的收缩或舒张反应,这可能是通过促进各种兔组织神经末梢神经递质的释放。研究表明,内源性大麻素系统和烟碱系统之间存在相互作用。本研究旨在探讨尼古丁与兔膀胱内源性大麻素系统之间的相互作用,以及尼古丁对兔离体膀胱平滑肌 EFS 诱导的收缩反应的增强作用及其与内源性大麻素系统的相互作用。
本研究使用新西兰白兔成年雄性。在划痕后,迅速切除膀胱,然后制备均匀的条带。每条条带在含有 20 mL Krebs-Henseleit 溶液的器官浴中以 1 g 等长静息张力下安装。在获得 EFS 诱导的收缩反应后,将 10-4 M 浓度的尼古丁应用于制剂,并且在 5 次刺激后停止 EFS。洗涤后,用相同的实验程序在存在 AM251(大麻素 CB1R 拮抗剂,10-6 M)、AM630(大麻素 CB2R 拮抗剂,10-6 M)和辣椒素(香草素受体拮抗剂,3×10-6 M)的情况下对相同的组织进行相同的实验。
尼古丁以 4-Hz 刺激频率增强了 17.16%±2.81%的 EFS 诱导的收缩反应。大麻素受体拮抗剂 AM251 和 AM630 降低了尼古丁的这种增强作用,尽管不显著,而香草素受体拮抗剂辣椒素并未显著改变尼古丁的作用。
这些结果表明,即使不显著,内源性大麻素系统也可能在尼古丁的作用中发挥作用,从而增强尼古丁对兔膀胱平滑肌的作用。