Effects of cannabinoid and vanilloid receptor antagonists on nicotine induced relaxation response enhancement in rabbit corpus cavernosum

Objective(s): 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 (۳×۱۰−۵ M). After contraction reached a plateau, strips were stimulated with EFS, and with the stabilization of EFS relaxation responses, ۱۰-۴  M of nicotine was administered to tissues. After that, in order to investigate the effects of AM۲۵۱ (CB۱ antagonist), AM۶۳۰ (CB۲ inverse agonist) or capsazepine (a vanilloid receptor antagonist) were given to different tissues, after the resting period.Results: Nicotine (۱۰−۴ M) increased the EFS-induced relaxation responses (۱۴.۶۰%±۲.۹۴%, P<۰.۰۵). AM۶۳۰ decreased the enhancement of nicotine-induced EFS relaxation responses (nicotine ۱۰-۴ M enhancement: ۱۷.۱۶%±۳.۱۹%; nicotine ۱۰-۴ M enhancement in the presence of AM۶۳۰ ۱۰-۶ M: ۴.۴۴%±۳.۴۳% P<۰.۰۵; n=۶), whereas effects of AM۲۵۱ 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 CB۲ receptors but not CB۱ and VR۱ receptors.

Keywords:

Cannabinoid receptors , Endocannabinoids , Nicotine , Penile erection , Smooth Muscle