Effect of vanilloid drugs on gastrointestinal transit in mice

Abstract

1. 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. 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.) 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)). 3. 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. 4. 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)). 5. 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.

Figure 1

Effect of i.p.-injected anandamide and piperine on upper gastrointestinal transit. Each point represents the mean±s.e.mean of six animals for each experimental group. ^*P<0.05, ^**P<0.01 and ^***P<0.001 vs corresponding control.

Figure 2

Effect of piperine (10 mg kg⁻¹, i.p.) or anandamide (10 mg kg⁻¹) on upper gastrointestinal transit alone or in mice treated with the cannabinoid CB₁ receptor antagonist SR141716A (SR1, 0.3 mg kg⁻¹ i.p.) or the vanilloid receptor antagonist capsazepine (CPZ, 15 mg kg⁻¹, i.p.). Results are mean±s.e.mean of 7 – 8 animals for each experimental group. ^*P<0.05 and ^**P<0.01 vs control and #P<0.01 vs anandamide (alone).

Figure 3

Effect of piperine (10 mg kg⁻¹ i.p.) or anandamide (10 mg kg⁻¹ i.p.) on upper gastrointestinal transit in mice not receiving capsaicin or in capsaicin (75 mg kg⁻¹ s.c., 13 and 14 days before)-treated mice. Each point represents the mean±s.e.mean of 7 – 8 animals for each experimental group. ^*P<0.05 and ^**P<0.01 vs corresponding control (animals not treated with anandamide or piperine) and #P<0.05 vs piperine.

Figure 4

Effect of piperine (10 mg kg⁻¹, i.p.) or anandamide (10 mg kg⁻¹ i.p.) on upper gastrointestinal transit alone or in mice treated with naloxone (NLX, 2 mg kg⁻¹, i.p.), yohimbine (YOH, 1 mg kg⁻¹ i.p.), N^G-nitro-L-arginine methyl ester (L-NAME, 25 mg kg⁻¹) and hexamethonium (HEX, 1 mg kg⁻¹ i.p.). Results are mean±s.e.mean of 7 – 8 animals for each experimental group. ^*P<0.05 and ^**P<0.01 vs control.