Functional Characterization of Nonadrenergic Noncholinergic Neurotransmitter Release via Endocannabinoids: An in Vitro Study in Rabbit Corpus Cavernosum

Abstract

Corporal smooth muscle relaxation is mediated mainly but not completely by nitric oxide. Endocannabinoids modulate the various neurotransmitter systems. In the present study, a possible role of endocannabinoids on non-nitrergic nonadrenergic noncholinergic (NANC)-mediated relaxations was investigated. In precontracted tissues, control electrical field stimulation (EFS)-induced NANC relaxation responses were obtained using varying frequencies of stimulation in the presence of L-arginine methyl ester (L-NAME), guanethidine, and atropine. To investigate the effects of cannabinoids on EFS-evoked non-nitrergic NANC relaxation responses, a similar experimental procedure was applied in the presence of cannabinoid receptor antagonists AM251 or AM630; vanilloid receptor antagonist capsazepine; or cannabinoid receptor agonists anandamide, arachidonyl-2-chloroethylamide (ACEA), or JHW015. Effects of cannabinoid receptor antagonists and agonists on EFS-evoked non-nitrergic NANC relaxation responses. L-NAME abolished EFS-induced relaxation responses at lower frequencies (2-4 Hz) and inhibited the relaxation responses at higher frequencies (8-32 Hz). AM251 and AM630 either together or separately inhibited, whereas anandamide, ACEA, and JHW015 enhanced non-nitrergic NANC relaxation responses. Anandamide did not alter EFS-induced non-nitrergic NANC relaxations in the presence of AM251 and AM630. Capsazepine enhanced non-nitrergic NANC relaxation responses. These results suggest that non-nitrergic NANC relaxations may be mediated partially by cannabinoid-like neuronal factors acting at both cannabinoid CB(1) and cannabinoid CB(2) receptors.