Prostaglandin EP Receptor Subtypes Involved in Regulating HCO3- Secretion from Gastroduodenal Mucosa

Author(s): Koji Takeuchi , Masafumi Koyama , Shusaku Hayashi , Eitaro Aihara .

Journal Name: Current Pharmaceutical Design

Volume 16 , Issue 10 , 2010

Abstract:

Gastroduodenal HCO3 - secretion is a key process that aids in preventing acid-peptic injury. The HCO3 - secretion in rats and mice was increased in response to PGE2 as well as mucosal acidification, the latter response occurring with a concomitant enhancement of mucosal PG production. The duodenal responses to PGE2 and acid were decreased in mice lacking EP3 receptors and reduced by coadministration of an EP3 or EP4 antagonist in rats, complete inhibition being observed when the EP3 and EP4 antagonists were given together. By contrast, the gastric responses disappeared in EP1-knockout mice and were prevented by an EP1 antagonist but not other EP antagonists. Furthermore, duodenal HCO3 - secretion was stimulated by the EP3 and EP4 agonists, whereas gastric HCO3 - secretion was increased only by the EP1 agonist. In addition, the HCO3 - stimulatory effect of sulprostone (an EP1/EP3 agonist) in the duodenum was inhibited by verapamil, a Ca2+ antagonist, and enhanced by isobutyl- methylxanthine, a phosphodiesterase (PDE) inhibitor, but the response in the stomach was inhibited by verapamil and not affected by isobutylmethylxanthine. In the mouse duodenum but not stomach, the response to PGE2 was potentiated by both vinpocetine (a PDE1 inhibitor) and cilostamide (a PDE3 inhibitor). These results suggest that the HCO3 - stimulatory effect of PGE2 in the duodenum is mediated by both EP3 and EP4 receptors, being coupled intracellularly with Ca2+ and cAMP, while that in the stomach is mediated by EP1 receptors, coupled with Ca2+. In addition, both PDE1 and PDE3 are involved in the regulation of duodenal HCO3 - secretion.

Keywords: HCO3 - secretion, stomach, duodenum, prostaglandin EP receptor subtypes, mucosal protection

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Article Details

VOLUME: 16
ISSUE: 10
Year: 2010
Page: [1241 - 1251]
Pages: 11
DOI: 10.2174/138161210790945931
Price: $58

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