Stimulation by nizatidine, a histamine H2-receptor antagonist, of duodenal HCO3- secretion in rats: relation to anti-cholinesterase activity

Figure 1 Effect of nizatidine on duodenal HCO₃^- secretion in rats. The HCO₃^- secretion was measured by perfusing a duodenal loop with saline and by adding 10 mM HCl to the reservoir. Nizatidine (3-30 mg/kg) was administered i.v. as a single injection after the basal secretion had well stabilized, and the HCO₃^- secretion was measured f or 2 h. Data are expressed as % of basal values and represent the means ± SE of values determined every 15 min from 6 rats. Lower panel shows △increase of HCO₃^- output for 2 h. Data are presented as the means ± SE from 6 rats. ^aSignificant difference from controls, P < 0.05.

Figure 2 Effects of neostigmine, carbachol and famotidine on duodenal HCO₃^- secretion in rats. The HCO₃^- secretion was measu red by perfusing a duodenal loop with saline and by adding 10 mM HCl to the reservoir. Neostigmine (0.03 mg/kg), carbachol (0.01 mg/kg) or famotidine (10 mg/kg) was administered i.v. as a single injection after the basal secretion had well stabilized, and the HCO₃^- secretion was measured for 2 h. Data are expressed as % of basal values and represent the means ± SE of values determined every 15 min from 6 rats. Lower panel shows △ increase of HCO₃^- output for 2 h. Data are presented as the means ± SE from 6 rats. ^aSignificant difference from controls, P < 0.05.

Figure 3 Effect of cisapride on duodenal HCO₃^- secretion in rats. The HCO₃^- secretion was measured by perfusing a duodenal loop with saline and by adding 10 mM HCl to the reservoir. Cisapride (3 mg/kg) was administered i.v. as a single injection after the basal secretion had well stabilized, and the HCO₃^- secretion was measured for 2 h. Data indicate total HCO₃^- output obtained for 2 h after administration of cisapride, and represent the means ± SE from 6 rats.

Figure 4 Effects of atropine or bilateral vagotomy on the HCO₃^- stimulatory action of nizatidine, neostigmine and carbachol in the rat duodenum. The HCO₃^- secretion was measured by perfusing a duodenal loop with saline and by adding 10 mM HCl to the reservoir. Neostigmine (0.03 mg/kg), carbachol (0.01 mg/kg) or famotidine (10 mg/kg) was administered i.v. as a single injection after the basal secretion had well stabilized, and the HCO₃^- secretion was measured for 2 h. Atropine (1 mg/kg) was given s.c. 1 h before admin istration of the above agents. Bilateral vagotomy was performed acutely at the cervical portion 2 h before the administration of the agents. Data are presented as the means ± SE from 6 rats. Significant difference at P < 0.05; ^afrom corresponding groups without atropine; ^bfrom corresponding values observed for 1 h before the treatment (time: -60-0 min)

Figure 5 Effects of nizatidine and acetylcholine, either alone or in combination, on duodenal HCO₃^- secretion in rats. The HCO₃^- secretion was measured by perfusing a duodenal loop with saline and by adding 10 mM HCl to the reservoir. Nizatidine (3 mg/kg) and acetylcholine (0.003 mg/kg), either alone or in combination, were administered i.v. after the basal secretion had well stabilized, and the HCO₃^- secretion was measured for 2 h. Data are expressed as % of basal values and represe nt the means ± SE of values determined every 15 min from 6 rats. Lower panel shows △increase of HCO₃^- output for 2 h. Data are presented as the means ± SE from 6 rats. Significant difference at P < 0.05^a from control; ^bfrom nizatidine or acetylcholine.

Figure 6 Effects of nizatidine and famotidine on histamine-induced gastric acid secretion in rats. A rat stomach mounted in an ex-vivo chamber was perfused with saline, and the acid secretion was measur ed by adding 100 mM NaOH to the reservoir. The acid secretion was stimulate d by i.v. infusion of histamine (4 mg/kg/h), while nizatidine (10 and 30 mg/kg) or famotidine (10 mg/kg) was administered i.v. as a single injection 1 h after the onset of histamine infusion, when the acid secretion had reached a plateau. Data are presented as the means ± SE of values determined every 15 min from 5 rats. ^aSignificant difference from controls, P < 0.05.

Figure 7 Representative recordings of gastric motor activity in conscious rats, before and after administration of nizatidine. gastric motor activity was monitored as intraluminal pressure recordings, by using a miniature balloon placed in the stomach. Nizatidine (30 mg/kg) was administered i.v. as a single injection after the basal motility had well stabilized. Atropine (1 mg/kg) was given s.c. 1 h after administration of nizatidine. Note that gastric motor activity was apparently enhanced by nizatidine at the doses that stimulate HCO₃^- secretion in the rat duodenum, and this action was completely blocked by atropine.