Carbonic anhydrase in the normal rat stomach and duodenum and after treatment with omeprazole and ranitidine.
A low pH in the lumen of the stomach and duodenum stimulates gastroduodenal mucosal secretion of bicarbonate, particularly in the duodenum. Long-term deprivation of this acid stimulus might affect the ability of the mucosa to secrete bicarbonate, with a consequent decrease in mucosal protection against the acid. This could occur by 'down-regulation' of carbonic anhydrase (CA) activity in the bicarbonate-transporting cells. Levels of CA activity and amounts of CA isoenzymes in rat gastric and duodenal mucosa were determined by biochemical assay and histochemical and immunohistochemical staining. Control animals and animals pre-treated for 4-6 weeks with the histamine H2-receptor antagonist ranitidine (600 mg kg-1 daily) or the H+,K+-ATPase inhibitor omeprazole (28 mg kg-1 daily) were examined. Both drugs are potent inhibitors of gastric secretion of acid. Both gastric and duodenal mucosal total CA activity and the distribution of isoenzymes were very similar in control animals and animals treated with these drugs. In the stomach, CA II was found in the surface epithelial and parietal cells. In the duodenum both CA I and CA II were observed. The staining for CA I was restricted to a small number of villus cells which looked like ordinary duodenal enterocytes. CA II in the duodenum was found in all villus cells, except the goblet cells. The staining decreased gradually from the top to the bottom of the villi and was absent in the crypts. Duodenal bicarbonate secretion is dependent on mucosal CA activity, and the distribution of CA II thus suggests that this alkaline secretion is of villous rather than cryptal origin.
Lönnerholm
G
G
Department of Medical Pharmacology, Uppsala University, Sweden.
Knutson
L
L
Wistrand
P J
PJ
Flemström
G
G
D000818:Animals; D002256:Carbonic Anhydrases / Q000378:metabolism*; D004386:Duodenum / Q000201:enzymology*; D005455:Fluorescent Antibody Technique; D005753:Gastric Mucosa / Q000201:enzymology; D006651:Histocytochemistry; D007413:Intestinal Mucosa / Q000201:enzymology; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D010295:Parietal Cells, Gastric / Q000201:enzymology; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013270:Stomach / Q000201:enzymology*
D011899:Ranitidine; D002256:Carbonic Anhydrases; D009853:Omeprazole