Background/Aims: 

Carbon monoxide (CO) with free iron and biliverdin are generated from degradation of heme catalyzed by constitutive heme oxygenase (HO-2) and inducible HO-1. Particularly, HO-1 is recognized as the stress protein, which is up- regulated by various stresses and exerts a protective action against tissue injury. By the way, HCO₃^- secretion is one of protective mechanisms in the duodenum against acid stress. However, no information is available concerning the relation of HO-1/CO with HCO₃^- secretion. In the present study, we examined the effect of a CO donor on HCO₃^- secretion in the rat duodenum and investigated whether HO is involved in the physiological regulation of this secretion.

Methods: 

Male SD rats were used after 18 h fasting. Under urethane anesthesia, a proximal duodenal loop was perfused with saline, and HCO₃^- secretion was measured at pH 7.0 using a pH-stat method and by adding 2 mM HCl.

Results: 

Topical application of CORM-2 (a CO donor) significantly increased duodenal HCO₃^- secretion in a concentration dependent manner. The stimulatory effect of CORM-2 was significantly attenuated by indomethacin (a non-selective COX inhibitor) and acetazolamide (an inhibitor of carbonic anhydrase). The mucosal application of CORM-2 increased the PGE2 contents. The secretion of HCO₃^- was increased by acidification of the mucosa, in an indomethacin- inhibitable manner. The acid- induced HCO₃^- response was also markedly inhibited by SnPP (an inhibitor of HO).

Conclusions: 

These results suggest that CO stimulates HCO₃^- secretion in the duodenum, and this effect is mediated by endogenous PGE2 and partly dependent on CO₂ generated from the reaction of CO with O₂.