Cyclic AMP in gastric juice does not reflect histamine H2 receptor activity in Heidenhain pouch dog.
It is strongly believed that cAMP mediates histamine H2 receptor activity, but does not mediate gastrin and acetylcholine stimulation of gastric acid secretion. Therefore, cAMP production could be a marker of H2 receptor activity. Whether endogenous histamine mediates gastrin and/or acetylcholine stimulation, at least partially, remains to be elucidated. If cAMP in the gastric juice reflects H2 receptor activity, we can investigate whether endogenous histamine mediates gastrin and/or acetylcholine stimulation in vivo. In this study, we investigated whether cAMP in the gastric juice reflected histamine H2 receptor activity in the Heidenhain pouch dog in vivo using different kinds of inhibitors of gastric secretion. Our hypothesis was as follows: Upon betazole stimulation, cimetidine, an H2 receptor antagonist, should decrease cAMP output into the gastric juice, but omeprazole, an H+, K+-ATPase blocker, should not, because it blocks at a site more peripheral than the H2 receptor and the production of cAMP. Sixty minutes after betazole administration, 4.0 mumol/kg of cimetidine and 0.18 mumol/kg omeprazole were administered intravenously and they inhibited gastric juice volume to a similar degree, that is, 49.6% and 52.1%, respectively. However, omeprazole caused a greater decrease in cAMP output than cimetidine. Inhibition with 4 mumol/kg/h of cimetidine or 0.2 mumol/kg of omeprazole from the beginning of betazole stimulation also caused similar decreases in gastric juice volume, 66.6% and 60.6%, respectively. Both inhibitors decreased cAMP output into the gastric juice in a similar fashion in the first two 30 minute periods. These results do not agree with our hypothesis.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis*; D004285:Dogs; D005750:Gastric Juice / Q000032:analysis*; D009853:Omeprazole / Q000494:pharmacology; D011970:Receptors, Histamine H2 / Q000187:drug effects / Q000378:metabolism*; D013270:Stomach / Q000502:physiology*
D011970:Receptors, Histamine H2; D002927:Cimetidine; D000242:Cyclic AMP; D009853:Omeprazole