Published online Oct 15, 2000. doi: 10.3748/wjg.v6.i5.651
Revised: August 18, 2000
Accepted: August 25, 2000
Published online: October 15, 2000
AIM: To examine whether nizatidine stimulates duodenal HCO3- secretion in rats by inhibiting AChE activity.
METHODS: Under pentobarbital anesthesia, a proximal duodenal loop was perfused with saline, and the HCO3- secretion was measured at pH7.0 using a pH-stat method and by adding 10 mM HCl. Nizatidine, neostigmine, carbachol or famotidine was administered i.v. as a single injection.
RESULTS: Intravenous administration of nizatidine (3-30 mg/kg) dose-dependently increased duodenal HCO3- secretion, and the effect at 10 mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg. This nizatidine action was observed at the same dose range that inhibited acid secretion and enhanced gastric motility, mimicked by i.v. injection of neostigmine (0.03 mg/kg), and significantly attenuated by bilateral vagotomy and prior s.c. administration of atropine but not by indomethacin, a cyclooxygenase inhibitor, or NG-nitro-L-arginine methyl ester, a NO synthase inhibitor. The HCO3- secretory response to acetylcholine (0.001 mg/kg) was significantly potentiated by the concurrent administration of nizatidine (3 mg/kg, i.v.). The IC50 of nizatidine for AChE of rat erythrocytes was 1.4 × 10-6 M, about 12 times higher than that of neostigmine. Neither famotidine (> 10-3 M, 30 mg/kg, i.v.) nor cisapride (> 10-3 M, 3 mg/kg, i.v.) had any influence on AChE activity or duodenal HCO3- secretion. Duodenal damage induced by acid perfusion (100 mM HCl for 4 h) in the presence of indomethacin was significantly prevented by nizatidine and neostigmine, at the doses that increased the HCO3- secretion.
CONCLUSION: Nizatidine stimulates duodenal HCO3- secretion, in both vagal-dependent and atropine-sensitive manners, and the action is associated with the anti-AChE activity of this agent.