Aim: 

Endocannabinoids have been reported to influence gastric contractions. In the present experiments we investigated whether endocannabinoids also affect non-adrenergic, non-cholinergic (NANC) relaxant responses.

Methods: 

Gastric longitudinal strips from the fundus region were mounted in organ baths for isometric recording. Electrical field stimulation (EFS) was applied via two platinum wire rings.

Results: 

In carbachol precontracted strips, EFS elicited tetrodotoxin (TTX)-sensitive fast nitrergic relaxant responses that, at the highest stimulation frequencies, were followed by sustained relaxations. These latter were abolished by a-chymotrypsin that also increased the amplitude of the fast responses. Anandamide, an endogenous cannabinoid (CB) receptor ligand, caused a TTX-sensitive relaxation that was abolished by a-chymotrypsin but unaffected by the nitric oxide (NO) synthesis inhibitor, L-NNA. Anandamide reduced the amplitude of EFS-induced fast relaxations whereas increased that of sustained ones. Relaxation to the ganglionic stimulating agent DMPP was decreased in amplitude by either anandamide or L-NNA whereas, surprisingly, it was increased by a-chymotrypsin and abolished by L-NNA plus a-chymotrypsin. The CB1 receptor antagonist AM-251 increased, only at the highest stimulation frequencies, the amplitude of the EFS-induced fast relaxation and reduced the sustained one. AM-251 increased the response to DMPP. The CB2 receptor antagonist AM-630 had no effects.

Conclusions: 

These results indicate that endocannabinoids modulate, via postganglionic CB1 receptors, the NANC peptidergic neurotransmission that, in turn, affects the nitrergic one.