Possible mechanisms underlying the suppression of gastric vagal afferents due to ecabapide (DQ-2511), a gastroprokinetic agent, in rats.

We examined the implication of a nitric oxide (NO)-guanosine 3',5'-cyclic monophosphate (cGMP) cascade in the suppression of gastric vagal afferents due to ecabapide in anesthetized rats using a standard extracellular method of multi-unit recording. Sodium nitroprusside (SNP, 0.5 mg/kg), an NO donor, depressed the afferent discharge rate of the vagus nerve, like ecabapide (60 micrograms/kg). On the other hand, NG-nitro-L-arginine (L-NNA, 5 mg/kg), an NO biosynthesis inhibitor, significantly elevated its discharge rate. Pretreatment with L-NNA completely blocked the action of ecabapide. Atropine (0.05 mg/kg), a competitive antagonist of muscarinic cholinoceptors, showed no effect on the afferent firing. These results suggest that ecabapide may suppress the activation of vagal afferents in gastric inhibitory vago-vagal reflex pathways through the NO-cGMP cascade.