Relation of hypoxia inducible factor-1A to vasoactive factors during healing of gastric ulcers

Abstract

agoinst and antagonist, In the present study, we examined, using specific EP4 agonist and antagonist, the involvement of EP4 ~ceptors in the HCO~ secretory response in rat duodenums and investigated the intracellular signaling coupled with EP4 receptors, in comparison with that of EP3 receptors. Methods: Male SD rats were used aider 18 h fasting. Under urethane anesthesia, a proximal duodenal loop was perfused with saline, and the HCO3 secretion was measured at pH 7.0 using a pH-stat method and adding 10 mM HCI. PGE2 (1 ragg stimulatory action of ONOAE1-329 but not Sul was significantly attenuated ONO-AE3-208. Likewise, ONO-AE3208, the EP4 antagonist, partially but sign~l~cantly mitigated the HCO3 secretion in response to PGE2 as well as luminal acidification. [BMX potentiated the HCOf stimulatoty action of both Sul and ONO-AF1-329, while verapamil s~ginficantly mitigated the effect of Sul but not ONO-AE1-329 Sensory deatterentadon did not af|ect the H C Q secretion induced either Snl or ONO-AE1-329. Conclusion: These results suggest that 1) EP4 receptors are invob:,ed in the HCO~ stitmdamry action of PGE2 m rat duodenums, in addition to EP3 receptors, 2) the process of HCO~ secretion difffrs in second messenger coupling; the stinmlation through EP4 receptors is mediated cAMP, while that by EP3 receptors is mediated both cAMP and Ca ~ and 3) Sensory neurons have no interaction with the HCO~ stimulatory action of PGE2