Stimulation by nizatidine, a histamine H(2)-receptor antagonist, of duodenal HCO(3)(-)secretion in rats:relation to anti-cholinesterase activity.

AIM:To examine whether nizatidine stimulates duodenal HCO(3)(-) secretion in rats by inhibiting AChE activity.METHODS:Under pentobarbital anesthesia, a proximal duodenal loop was perfused with saline, and the HCO(3)(-) secretion was measured at pH 7.0 using a pH-stat method and by adding 10mM HCl. Nizatidine, neostigmine, carbachol or famotidine was administered i.v. as a single injection.RESULTS:Intravenous administration of nizatidine (3-30mg/kg) dose-dependently increased duodenal HCO(3)(-) secretion, and the effect at 10mg/kg was equivalent to that obtained by carbachol at 0.01mg/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(0.03mg/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 HCO(3)(-) secretory response to acetylcholine (0.001mg/kg) was significantly potentiated by the concurrent administration of nizatidine (3mg/kg,i.v.). The IC(50) 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, 30mg/kg, i.v.) nor cisapride (> 10(-3) M,3mg/kg, i.v.) had any influence on AChE activity or duodenal HCO(3)(-) secretion. Duodenal damage induced by acid perfusion (100mM HCl for 4h) in the presence of indomethacin was significantly prevented by nizatidine and neostigmine, at the doses that increased the HCO(3)(-)secretion.CONCLUSION:Nizatidine stimulates duodenal HCO(3)(-) secretion, in both vagal dependent and atropine sensitive manners, and the action is associated with the anti-AChE activity of this agent.