1. The influence of theophylline on the mucosa to serosa and serosa to mucosa fluxes of HCO3- were measured by the pH stat technique in isolated segments of proximal small intestine from Amphiuma maintained under short-circuited conditions. The mucosal or serosal fluid was exposed to media containing 25 mM-HCO3- (pH 7.4) while the pH of unbuffered media in the opposite compartment was maintained by addition of acid. 2. Theophylline significantly increased the secretory flux of HCO3- and significantly reduced the absorptive flux when measured in Cl- -free (SO4(2-)) media. 3. In normal media theophylline did not alter the secretory flux but significantly lowered the absorptive flux of HCO3-. 4. Acetazolamide (0.1 mM) inhibited the theophylline-stimulated secretory flux of HCO3- and reduced the effect of theophylline on the absorptive flux. 5. In normal intestine there was an inequality between the secretory or absorptive HCO3- flux and the short-circuit current (Isc) consistent with the presence of Cl- absorption. After addition of theophylline the Isc was more nearly equal to the net secretory or absorptive HCO3- flux. 6. Exogenous cyclic AMP had effects identical with theophylline. 7. The results provide strong evidence that elevation of cyclic AMP stimulates net HCO3- secretion in urodele small intestine and provide indirect evidence that Cl- absorption is simultaneously reduced.
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