It is well accepted that endogenous cannabinoids and CB1 receptors are involved in the regulation of smooth muscle contractility and intestinalmotility, through a mechanism mainly related to reduction of acetylcholine release from cholinergic nerve endings. Because, few data exist on apossible modulatory action of the cannabinoid agents on the non-adrenergic non-cholinergic (NANC) excitatory and inhibitory neurotransmission,the aim of the present study was to investigate the effects of cannabinoid drugs on the NANC responses elicited by electrical field stimulation(EFS) in the circular muscle of mouse proximal colon. Colonic contractions were monitored as changes in endoluminal pressure.In NANC conditions, EFS evoked TTX-sensitive responses, characterized by a relaxation, nitrergic in origin, followed by a contraction. TheEFS-evoked contraction was significantly reduced by SR48968, NK2 receptor antagonist, and abolished by co-administration of SR48968 andSR140333, NK1 receptor antagonist, suggesting that it was due to release of tachykinins. The cannabinoid receptor synthetic agonist, WIN55,212-2, the putative endogenous ligand, anandamide, the selective CB1 receptor agonist ACEA, but not the selective CB2 receptor agonist JWH-015,produced a concentration-dependent reduction of the NANC contractile responses, without affecting the NANC relaxation. ACEA or anandamidedid not modify the contractions induced by exogenous [-Ala8]-NKA(4–10), agonist of NK2 receptors. The selective antagonist of CB1 receptors,SR141716A, per se failed to affect the EFS-evoked responses, but antagonized the inhibitory effects of WIN55,212-2, anandamide and ACEA onNANC contractile responses. AM630, CB2 receptor antagonist, did not modify the inhibitory effects of WIN55,212-2 or anandamide. URB597,inhibitor of the fatty acid amide hydrolase, enzyme which catalyze the hydrolysis of anandamide, was without any effect on the NANC evokedresponses. We conclude that the activation of prejunctional CB1 receptors produces inhibition of NANC contractile responses in mouse colonicpreparations. However, endogenous ligands do not seem to modulate tonically the NANC transmission in mouse colon.
|Numero di pagine||8|
|Stato di pubblicazione||Published - 2007|
All Science Journal Classification (ASJC) codes