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.
Hatanaka
S
S
Tokyo Research and Development Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Niijima
A
A
Furuhama
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D006152:Cyclic GMP / Q000378:metabolism; D003864:Depression, Chemical; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects / Q000294:innervation*; D014630:Vagus Nerve / Q000187:drug effects*
D000897:Anti-Ulcer Agents; D001549:Benzamides; D004791:Enzyme Inhibitors; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; C058308:ecabapide; D019001:Nitric Oxide Synthase; D006152:Cyclic GMP