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[摘要]：We examined the effect of the tricarbonyl-dichlororuthenium (II) dimer (CORM-2), a carbon monoxide (CO) donor, on duodenal HCO3- secretion in rats and investigated whether endogenous CO produced by heme oxygenase (HO) is involved in the regulation of this secretion. Under urethane anesthesia, a duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 using a pH stat method. CORM-2, biliverdin, FeCl2,or ruthenium (III) chloride hydrate (RuCl3) was applied to the loop for 5 min. The mucosal application of CORM-2 dose-dependently increased HCO3- secretion, whereas neither RuCl3, FeCl2, nor biliverdin had an effect. The stimulatory effect was significantly attenuated by indomethacin but not NG-nitro-L-arginine methyl ester. The application of CORM-2 increased the mucosal prostaglandin (PG) E-2 content of the duodenum. The acid-induced HCO3- response was markedly inhibited by indomethacin and Sn(IV) protoporphyrin IX dichloride (SnPP; an inhibitor of HO) but not Cu(II) protoporphyrin dichloride, and the inhibitory effect of SnPP was significantly reversed by pretreatment with hemin, a substrate of HO. Perfusion of the duodenal loop with 100 mM HCl for 2 h caused a few hemorrhagic lesions in the mucosa, and this response was significantly worsened by the prior administration of SnPP and indomethacin. The expression of HO-1 but not HO-2 protein was up-regulated in the duodenum after the acid treatment. These results suggest that CO, generated endogenously or exogenously, stimulates HCO3- secretion in the duodenum, and this effect is mediated by endogenous PGs. It is assumed that HO/CO plays a role in maintaining the integrity of the duodenal mucosa. |
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