Carbon monoxide involved in modulating HCO3- secretion in rat duodenum.
We examined the effect of the tricarbonyl-dichlororuthenium (II) dimer (CORM-2), a carbon monoxide (CO) donor, on duodenal HCO(3)(-) 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 HCO(3)(-) secretion was measured at pH 7.0 using a pH stat method. CORM-2, biliverdin, FeCl(2), or ruthenium (III) chloride hydrate (RuCl(3)) was applied to the loop for 5 min. The mucosal application of CORM-2 dose-dependently increased HCO(3)(-) secretion, whereas neither RuCl(3), FeCl(2), nor biliverdin had an effect. The stimulatory effect was significantly attenuated by indomethacin but not N(G)-nitro-L-arginine methyl ester. The application of CORM-2 increased the mucosal prostaglandin (PG) E(2) content of the duodenum. The acid-induced HCO(3)(-) 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 HCO(3)(-) 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.
Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Kyoto, Japan.
Hironori
H
Takasuka
Shusaku
S
Hayashi
Masafumi
M
Koyama
Masashi
M
Yasuda
Eitaro
E
Aihara
Kikuko
K
Amagase
Koji
K
Takeuchi
D000818:Animals; D002248:Carbon Monoxide / Q000494:pharmacology* / Q000502:physiology*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D027982:Sodium-Bicarbonate Symporters / Q000378:metabolism*
D027982:Sodium-Bicarbonate Symporters; D002248:Carbon Monoxide