Inhibitory effect of palmitoylethanolamide on gastrointestinal motility in mice

Abstract

1. We have studied the effect of palmitoylethanolamide (PEA, 2.5 - 30 mg kg(-1), i.p.) on upper gastrointestinal transit in control mice and in mice with chronic intestinal inflammation induced by croton oil. 2. PEA significantly and dose-dependently decreased intestinal transit. The inhibitory effect of PEA (10 mg kg(-1)) was not modified by the cannabinoid CB(1) receptor antagonist SR141716A (0.3 mg kg(-1), i.p.), the cannabinoid CB(2) receptor antagonist SR144528 (1 mg kg(-1), i.p.), N(G)-nitro-L-arginine methyl ester (L-NAME, 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.). 3. PEA levels were significantly decreased in the small intestine of croton oil-treated mice. In these animals, PEA also inhibited motility and this effect was not counteracted by SR141716A (0.3 mg kg(-1)), or SR144528 (1 mg kg(-1)). 4. Pre-treatment of mice with the amidase inhibitor phenylmethyl sulphonil fluoride (PMSF, 30 mg kg(-1), i.p.) did not modify the inhibitory effect of PEA, either in control or in mice with inflammation. 5. It is concluded that PEA inhibits intestinal motility with a peripheral mechanism independent from cannabinoid receptor activation. The decreased levels of PEA in croton oil-treated might contribute, at least in part, to the exaggerated transit observed during chronic intestinal inflammation.

Figure 1

Inhibitory effect of palmitoylethanolamide (PEA, 2.5 – 30 mg kg⁻¹, i.p.) on upper gastrointestinal transit: effect of a pretreatment with the amidase inhibitor phenylmethyl sulphonil fluoride (PMSF, 30 mg kg⁻¹ i.p.). Results are mean±s.e.mean of 10 animals for each experimental group. ^*P<0.05, ^**P<0.01 vs control.

Figure 2

Croton oil-treated mice: effect of the amidase inhibitor phenylmethyl sulphonil fluoride (PMSF, 30 mg kg⁻¹ i.p.) on palmitoylethanolamide (PEA, 2.5 – 30 mg kg⁻¹, i.p.)-induced delay in upper gastrointestinal transit. Results are mean±s.e.mean of 10 animals for each experimental group. #P<0.05 vs control, ^*P<0.05 and ^**P<0.01 vs croton oil.

Figure 3

Levels of palmitoylethanolamide (PEA) in the mouse small intestine during control and croton oil-induced gut inflammation. Results are mean±s.e.mean of 4 – 5 animals for each experimental group. ^*P<0.05 vs control.