Background/aim: We investigated the role of prostacyclin (PGI2) IP receptors in the acid-induced secretion of HCO3- using IP receptor knockout [IP (-/-)] mice, in comparison with capsaicin-induced secretion.
Methods: Male C57/BL6 mice, both wild-type [WT] and [IP (-/-)], fasted for 18 h were used. Under urethane anesthesia, a proximal duodenal loop was perfused with saline, and the secretion of HCO3- was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. The secretion was stimulated by exposure of the loop to 10 mM HCl, capsaicin, PGE2 or cicaprost (a PGI2 agonist) for 10 min.
Results: PGE2 stimulated HCO3- secretion in both WT and IP (-/-) mice, while cicaprost increased it in WT but not IP (-/-) mice. Luminal acidification increased the mucosal level of PGE2 as well as 6-keto-PGF1alpha, yet stimulated HCO3- secretion in both WT and IP (-/-) mice, in an indomethacin-inhibitable and sensory neuron-dependent manners. Perfusion of the duodenum with 20 mM HCl for 4 h caused severe damage in WT mice pretreated with indomethacin, but not in control WT or IP (-/-) mice. Capsaicin increased duodenal HCO3- secretion in WT mice, in an indomethacin-sensitive manner, yet no such response was observed in the animals lacking IP receptors.
Conclusion: The presence of IP receptors is not essential for acid-induced HCO3- secretion and mucosal defense against acid injury in the duodenum, although activation of IP receptors results in stimulation of HCO3- secretion. Although duodenal HCO3- secretion induced by both acid and capsaicin depends on afferent neurons, it seems that the mode of interaction with the afferent neurons differs regarding dependency on the PGI2/IP receptors.