Effects of Cholera Toxin and Phosphodiesterase Inhibitors on Fluid Transport and Cyclic Adenosine 3',5'-Monophosphate Concentrations in Rabbit Gallbladder

Abstract

The effects of cholera enterotoxin on fluid transport and on mucosal cyclic AMP content were investigated in the rabbit gallbladder. Gallbladders injected intraluminally with cholera toxin (0.1 or 10 μg in Krebs-bicarbonate buffer) exhibited markedly depressed rates of fluid absorption when excised 2 hr later and studied in vitro. The inhibition of absorption observed in gallbladders exposed to these doses of cholera toxin was accompanied by a significant (approximately 3.5-fold) increase in mucosal cyclic AMP content compared with control bladders. There was no significant difference between the effects of 0.1- and 10-μg doses of cholera toxin on either fluid transport or cyclic AMP content. The presence of 10 m m theophylline or 0.1 m m papaverine, both of which are phosphodiesterase inhibitors, in the solutions bathing the gallbladders also resulted in depressed rates of fluid transport and increased mucosal cyclic AMP content compared with control bladders. Significantly depressed rates of fluid transport were also observed when 3 m m cyclic AMP was present in the bathing solutions. The transmural electrical potential difference in the rabbit gallbladder was found to be close to 0 and unaffected by exposure to theophylline or papaverine.