Bicarbonate stimulatory action of nizatidine, a histamine H(2)-receptor antagonist, in rat duodenums.

Abstract

Nizatidine, a histamine H(2)-antagonist, is known to inhibit acetylcholinesterase (AChE) activity and is used clinically as a gastroprokinetic agent as well as the anti-ulcer agent. We examined whether or not nizatidine stimulates duodenal HCO(3)(-) secretion in rats through vagal-cholinergic mechanisms by inhibiting AChE activity. 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 10 mM HCl. Nizatidine, neostigmine, carbachol, famotidine or ranitidine was administered i.v. as a single injection. Intravenous administration of nizatidine (3-30 mg/kg) dose-dependently increased the HCO(3)(-) secretion, and the effect at 10 mg/kg was equivalent to that obtained by carbachol at 0.01 mg/kg. The HCO(3)(-) stimulatory action of nizatidine was observed at the doses that inhibited the histamine-induced acid secretion and enhanced gastric motility. This effect was mimicked by neostigmine (0.03 mg/kg) and significantly attenuated by bilateral vagotomy and pretreatment with atropine but not indomethacin. The IC(50) of nizatidine for AChE of rat erythrocytes was 1.4 x 10(-6) M, about 12 times higher than that of neostigmine. Ranitidine showed the anti-AchE activity and increased duodenal HCO(3)(-) secretion, similar to nizatidine, whereas famotidine had any influence on neither AChE activity nor the HCO(3)(-) secretion. On the other hand, 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 HCO(3)(-) secretion. These results suggest that nizatidine increases HCO(3)(-) secretion in the rat duodenum, mediated by vagal-cholinergic mechanism, the action being associated with the anti-AChE activity of this agent.

• Authors: H Mimaki, S Kawauchi, S Kagawa, S Ueki, K Takeuchi
• Journal: Journal of physiology, Paris (J Physiol Paris) 2001 Jan-Dec Vol. 95 Issue 1-6 Pg. 165-71 ISSN: 0928-4257 [Print] France
• PMID: 11595432 (Publication Type: Journal Article)

Chemical References

• Bicarbonates
• Histamine H2 Antagonists
• Acetylcholinesterase
• Nizatidine
• Hydrochloric Acid

Topics

• Acetylcholinesterase (metabolism)
• Animals
• Bicarbonates (metabolism)
• Duodenum (drug effects, metabolism, pathology)
• Gastric Acid (metabolism)
• Gastrointestinal Motility (drug effects)
• Histamine H2 Antagonists (pharmacology)
• Hydrochloric Acid (pharmacology)
• Male
• Nizatidine (pharmacology)
• Rats
• Rats, Sprague-Dawley