Effect of vanilloid drugs on gastrointestinal transit in mice

We have studied the effect of capsaicin, piperine and anandamide, drugs which activate vanilloid receptors and capsazepine, a vanilloid receptor antagonist, on upper gastrointestinal motility in mice. Piperine (0.5 – 20 mg kg −1 i.p.) and anandamide (0.5 – 20 mg kg −1 i.p.), dose‐dependently delayed gastrointestinal motility, while capsaicin (up to 3 mg kg −1 i.p.) was without effect. Capsazepine (15 mg kg −1 i.p.) neither per se affected gastrointestinal motility nor did it counteract the inhibitory effect of both piperine (10 mg kg −1 ) and anandamide (10 mg kg −1 ). A per se non effective dose of SR141716A (0.3 mg kg −1 i.p.), a cannabinoid CB 1 receptor antagonist, counteracted the inhibitory effect of anandamide (10 mg kg −1 ) but not of piperine (10 mg kg −1 ). By contrast, the inhibitory effect of piperine (10 mg kg −1 ) but not of anandamide (10 mg kg −1 ) was strongly attenuated in capsaicin (75 mg kg −1 in total, s.c.)‐treated mice. Pretreatment of mice with N G ‐nitro‐ L ‐arginine methyl ester (25 mg kg −1 i.p.), yohimbine (1 mg kg −1 , i.p.), naloxone (2 mg kg −1 i.p.), or hexamethonium (1 mg kg −1 i.p.) did not modify the inhibitory effect of both piperine (10 mg kg −1 ) and anandamide (10 mg kg −1 ). The present study indicates that the vanilloid ligands anandamide and piperine, but not capsaicin, can reduce upper gastrointestinal motility. The effect of piperine involves capsaicin‐sensitive neurones, but not vanilloid receptors, while the effect of anandamide involves cannabinoid CB 1 , but not vanilloid receptors.British Journal of Pharmacology (2001) 132 , 1411–1416; doi: 10.1038/sj.bjp.0703975