Effect of theophylline on l-alanine absorption in the rat jejunum

The effect of theophylline on the accumulation of L-alanine (Ala) by the rat jejunum and the mechanism involved has been investigated. Ala is rapidly accumulated by the jejunal strips in vitro and saturation is reached between 10 and 15 min. An In/Out ratio of 2.55 reflects the presence of an active component in the overall transport mechanism. Ala accumulation shows a tendency toward saturation as cellular Ala concentration increases. In the absence of Na+, Ala accumulation is reduced and a direct relationship is observed between alanine concentration in the incubation medium and its intracellular concentration. Alanine accumulation is inhibited when theophylline (TH) concentration in the incubation medium is greater than 0.5 mM. A maximum inhibition of approximately 50% in the presence of 10 mM theophylline is observed. Further inhibition (57-65%) is observed when the jejunal strips are incubated in a Na+-free medium containing 10 mM theophylline. Single-pass perfusion of the rat jejunum shows that the presence of 0.5 mM TH in the perfusate, simulating therapeutic doses, did not affect Ala absorption. However, about 55% inhibition of Ala absorption was observed when 10 mM TH was included in the perfusate. In conclusion, it could be stated that in both in vitro and in vivo studies high toxic but not therapeutic doses of TH inhibit intestinal Ala uptake. The mechanism of inhibition may be attributed to a non-carrier mediated mechanism with a minor effect noticed on Ala carrier system.