ABSTRACT
Objectives: Endocannabinoids and nicotine regulate the neurotransmitter release in different central and peripheral synapses. Various studies in the literature demonstrate the interaction between endocannabinoid and nicotinic systems, especially in the central nervous system. The interaction between nicotinic and endocannabinoid systems was investigated in this study. We aimed to show the effects of cannabinoid and vanilloid receptor antagonists on nicotine-induced relaxation response increases in rabbit corpus cavernosum. Materials and Methods: From a total of seven male albino rabbits, three or four equal strips were cut from each corpus cavernosum and inserted in isolated organ baths. Tissues were contracted with phenylephrine (3×10-5 M). After contraction reached a plateau, strips were stimulated with EFS, and with the stabilization of EFS relaxation responses, 10-4 M of nicotine was administered to tissues. After that, in order to investigate the effects of AM251 (CB1 antagonist), AM630 (CB2 inverse agonist) or capsazepine (a vanilloid receptor antagonist) were given to different tissues, after the resting period. Results: Nicotine (10-4 M) increased the EFS-induced relaxation responses (14.60%±2.94%, P<0.05). AM630 decreased the enhancement of nicotine-induced EFS relaxation responses (nicotine 10-4 M enhancement: 17.16%±3.19%; nicotine 10-4 M enhancement in the presence of AM630 10-6 M: 4.44%±3.43% P<0.05; n=6), whereas effects of AM251 and capsazepine were not significant. Conclusion: In the present study, nicotine increased the amplitudes of EFS-induced relaxation responses probably via nicotinic acetylcholine receptors located on the nitrergic nerves of the corpus cavernosum. We showed the role of cannabinoid-like endo-ligands in nicotine-induced enhancement via CB2 receptors but not CB1 and VR1 receptors.
ABSTRACT
BACKGROUND: 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. METHODS: 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). RESULTS: 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. DISCUSSION: 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.
