Stimulation of duodenal bicarbonate secretion by carbenoxolone in rats: a comparative study with prostaglandin E2.
1. The effects of carbenoxolone on duodenal HCO3- secretion were examined in anesthetized rats and compared with those of prostaglandin E2 (PGE2). 2. After 18-hr fasting, the duodenal loop (1.7 cm) that was made between the pyloric ring and the area just proximal to the outlet of the common bile duct was perfused with saline (pH 4.5), the pH of perfusate and the transmucosal potential difference (PD) were continuously monitored and HCO3- output was determined by titration with 10 mM HCl. 3. Under these conditions, duodenal pH, PD, and HCO3- secretion were increased in response to PGE2 (0.3 and 1.0 mg/kg) given intravenously as a single injection. Carbenoxolone (0.1-1.0 mg/kg, intravenously) also caused an increase in duodenal pH and HCO3- output in a dose-dependent manner, with a concomitant rise in PD; at 1 mg/kg, the magnitude of HCO3- output was almost equivalent to that induced by PGE2 at 0.3 mg/kg. 4. Prior administration of indomethacin, a cyclooxygenase inhibitor (5 mg/kg, subcutaneously), did not affect the HCO3- stimulatory action of carbenoxolone or PGE2. 5. Duodenal HCO3- secretion was also increased by intravenous injection of dibutylyl adenosine 3',5'-cyclic monophosphate (dbcAMP) but not by isobutylmethyl xanthine (IBMX; 10 mg/kg), an inhibitor of phosphodiesterase, but the former action was significantly potentiated in the presence of IBMX. Likewise, the pretreatment of IBMX significantly enhanced the HCO3- stimulatory action of PGE2 but had no effect on the HCO3- response induced by carbenoxolone. 6. These results suggest that carbenoxolone stimulates duodenal HCO3- secretion in rats, similar to PGE2 and this mechanism does not involve endogenous prostaglandins and is not associated with the intracellular accumulation of cAMP.
Takeuchi
K
K
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Kyoto, Japan.
Yagi
K
K
Kitamura
M
M
Kubomi
M
M
D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001639:Bicarbonates / Q000378:metabolism*; D002229:Carbenoxolone / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D000897:Anti-Ulcer Agents; D001639:Bicarbonates; D015232:Dinoprostone; D002229:Carbenoxolone