nitroarginine and ecabapide

Junctional transmissions and their modulation by DQ-2511, a novel prokinetic agent, were investigated in smooth muscle of the guinea pig duodenum. Transmural nerve stimulation evoked a cholinergic excitatory junction potential, a nonadrenergic, noncholinergic inhibitory junction potential, and a substance P mediated slow depolarization. DQ-2511 showed dual effects on the slow depolarization: a low concentration (10(-9) mol/l) enhanced and high concentrations (>10(-6) mol/l) tended to inhibit. The depolarization produced by exogenously applied substance P was enhanced by low concentrations of DQ-2511. The results suggest that the prokinetic actions of DQ-2511 involve an enhancement of transmission from substance P neurons due to an increase in sensitivity of postjunctional receptors to substance P.

Topics: Analgesics; Animals; Anti-Ulcer Agents; Apamin; Atropine; Autonomic Agents; Benzamides; Duodenum; Electric Stimulation; Enzyme Inhibitors; Excitatory Postsynaptic Potentials; Guanethidine; Guinea Pigs; In Vitro Techniques; Male; Membrane Potentials; Muscle, Smooth; Neuromuscular Junction; Nitroarginine; Substance P; Synaptic Transmission

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.

Topics: Animals; Anti-Ulcer Agents; Benzamides; Cyclic GMP; Depression, Chemical; Enzyme Inhibitors; Gastrointestinal Motility; Male; Neurons, Afferent; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Nitroprusside; Rats; Rats, Wistar; Stomach; Vagus Nerve