The influence of luminal pH on transport of neutral and charged dipeptides by rat small intestine, in vitro

Four hydrolysis-resistant dipeptides (D-phenylalanyl-L-alanine, D-phenylalanyl-L-glutamine, D-phenylalanyl-L-glutamate and D-phenylalanyl-L-lysine) were synthesized to investigate the effects of net charge on transmural dipeptide transport by isolated jejunal loops of rat small intestine. At a luminal pH of 7.4 and a concentration of 1 mM the two dipeptides with a net charge of - 1 and + 1 were transported at substantially slower rates (18 ± 1.3 and 8.4 ± 1.3 nmol min^-1 (g dry wt.)^-1, respectively) than neutral D-phenylalanyl-L-alanine and D-phenylalanyl-L-glutamine (87 ± 0.2 and 197 ± 14 nmol min^-1 (g dry wt.)^-1, respectively). We investigated the effects of luminal pH on dipeptide transport by varying the NaHCO₃ content of Krebs Ringer perfusate equilibrated with 95%O₂/5% CO₂. The pH changes did not affect water transport, but serosal glucose appearance increased significantly at pH 6.8. Transmural transport of D-phenylalanyl-L-alanine and D-phenylalanyl-L-glutamine at pH 6.8 was stimulated (P < 0.01) by 61% and 49%, respectively, whereas the lower pH increased the rate for negatively charged D-phenylalanyl-L-glutamate by 306% (P < 0.01) and decreased that for positively charged D-phenylalanyl-L-lysine by 46% (P < 0.05). Increasing luminal pH to 8.0 inhibited D-phenylalanyl-L-alanine transport by 60%, whereas D-phenylalanyl-L-lysine transport was 60% faster.