Background/Aim: 

The secretion of HCO₃^- from the surface epithelial cells is an important process to prevent acid-peptic injury. The mechanism of HCO₃^- secretion involves various types of ion channels and transporters, including chloride channels. Lubiprostone, a possible chloride channel type-2 (ClC-2) opener, is derived from prostaglandin E1 and used for the treatment of chronic constipation. Recently, this agent was reported to stimulate HCO₃^- secretion in the duodenum. However, it remains unknown whether or not lubiprostone affects the secretion of HCO₃^- in the stomach. In the present study, we examined the effect of lubiprostone on HCO₃^- secretion in the mouse stomach in vitro, focusing on the possible involvement of prostaglandin EP receptor activation.

Methods: 

Male C57BL/6J mice were used after 18 h fasting. The gastric mucosa, stripped of the muscular layers, was mounted on an Ussing chamber. HCO₃^- secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl. Lubiprostone (10^-4-3*10^­4 M) was applied to the serosal side. EP1 (10^-6–10^­5M) and EP4 (10^­6 M) antagonists were added serosally 30 min before the addition of lubiprostone. The mRNA expression of ClC-2 was investigated by RT-PCR.

Results: 

Lubiprostone stimulated gastric HCO₃^- secretion in a concentration- dependent manner. The HCO₃^- stimulatory action of lubiprostone was inhibited by EP1 antagonist but not EP4 antagonist. Furthermore, indomethacin (a non selective inhibitor) did not affect the increased HCO₃^- response to lubiprostone. The expression of ClC-2 channel mRNA was observed in the mouse gastric mucosa.

Conclusions: 

These results suggest that lubiprostone stimulates HCO₃^- secretion in the stomach, and this effect is mediated by the activation of EP1 receptors but not dependent on endogenous PG production.