Effect of vanilloid drugs on gastrointestinal transit in mice

1 We have studied the effect of capsaicin, piperine and anandamide, drugs w hich activate vanilloid receptors and capsazepine, a vanilloid receptor ant agonist, on upper gastrointestinal motility in mice. 2 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.) neith er pel se affected gastrointestinal motility nor did it counteract the inhi bitory effect of both piperine (10 mg kg(-1)) and anandamide (10 mg kg(-1)) . 3 A per se non effective dose of SR141716A (0.3 mg kg(-1) i.p.), a cannabin oid CBI receptor antagonist, counteracted the inhibitory effect of anandami de (10 mg kg(-1)) but not of piperine (10 mg kg(-1)). By contrast, the inhi bitory effect of piperine (10 mg kg(-1)) but not of anandamide (10 mg kg(-1 )) wa's strongly attenuated in capsaicin (75 mg kg(-1) in total, s.c.)-trea ted mice. 4 Pretreatment of mice with NG-nitro-L-arginine methyl eater (25mg kg(-1) i .p.), yohimbine (1 mg kg(-1), i.p.), naloxone (2 mg kg(-1) i.p.), or hexame thonium (1 mg kg(-1) i.p.) did not modify the inhibitory effect of both pip erine (10 mg kg(-1)) and anandamide (10 mg kg(-1)). 5 The present study indicates that the vanilloid ligands anandamide and pip erine, but not capsaicin, can reduce upper gastrointestinal motility. The e ffect of piperine involves capsaicin-sensitive neurones, but not vanilloid receptors, while the effect of anandamide involves cannabinoid CB1, but not vanilloid receptors.