Effect of long-term H2-blocker treatment on carbonicanhydrase in rat gastroduodenal mucosa Kazumasa Miyake Department of Hygiene and Public Health, Ni
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1 Effect of long-term H2-blocker treatment on carbonicanhydrase in rat gastroduodenal mucosa Kazumasa Miyake Department of Hygiene and Public Health, Nippon Medical School Famotidine, one of the histamine H2-receptor antagonists (H2-blockers), contains a sulfamoylamidine group. The sulfamoylamidine group contains a residue which is structurally similar to the sulfonamide group. This group is known to have a carbonic anhydrase (CA) inhibitory action. In the present study, it was confirmed that famotidine inhibited CA activity in vitro whereas cimetidine and ranitidine which lack sulfonamide-like residues did not. Considering these characteristics of the H2-blockers, the effects of long-term administration of the H2-blockers on CA activity in gastric and duodenal mucosa were examined using the H2-blockers with or without CA-inhibiting action. After male adult Wistar rats were treated for 4 weeks with famotidine (1.6mg/kg/day; F group) or cimetidine (32mg/kg/day; C group), CA activity in the mucosa from the antrum, fundus or duodenum was measured on the 1st, 3rd, 7th, 14th or 21st day after the last administration. In spite of CA inhibitory action of famotidine in vitro, CA activity was not lower in the mucosal preparations from F group than in those from C group. Although CA activity in the duodenal mucosa was not significantly different from that in the control, CA activity in the gastric mucosa of both C and F groups clearly showed a decreasing tendency. These results suggest that long-term treatment with H2-blockers might diminish mucosal protection efficacy through mechanisms other than the direct CA inhibitory action. Key words: histamine H2-receptor antagonists, carbonic anhydrase, mucosal protection Correspondence to Kazumasa Miyake, Department of Hygiene and Public Health, Nippon Medical School, Sendagi, Bunkyo-ku, Tokyo 113, Japan
2 Sulfonamide Famotidine Cimetidine Ranitidine Fig. 1 Structures of sulfonamide and three H2- blockers
3 Fig. 2 Effect of H2-blocker on purified human carbonic anhydrase and dose-response relation- ship between H2-blocker and carbonic anhy- drase activity. The values plotted are the means of one representative experiment in duplicate. Fig. 3 CA activity in rat duodenal mucosa treated with saline (control), famotidine or cimetidine. The samples were taken on 1, 3, 7, 14 or 21 days after last administration of the drug. Height of each bar represents the mean }SD (n= 6). Statistical evaluation was done by the Students's t-test.
4 Fig. 4 CA activity in rat antral mucosa treated with saline (control), famotidine or cimetidine. The samples were taken on 1, 3, 7, 14 or 21 days after last administration of the drug. Height of each bar represents the mean }SD (n=6). Statistical evaluation was done by the Student's t-test. Fig. 5 CA activity in rat fundic mucosa treated with saline (control), famotidine or cimetidine. The samples were taken on 1, 3, 7, 14 or 21 days after last administration of the drug. Height of each bar represents the mean }SD (n=6). Statistical evaluation was done by the Student's t-test.
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