Transport characteristics of 5-aminosalicylic acid into colonic epithelium: Involvement of sodium-coupled monocarboxylate transporter SMCT1-mediated transport system.

5-Aminosalicylic acid (5-ASA) is conventionally used as a first line drug for inflammatory bowel disease (IBD). Because 5-ASA is well absorbed in the small intestine, very high dose of 5-ASA is required to deliver it to the large intestine which is a target site. Interestingly, 5-ASA is reported to be transported into the large intestine as well as the small intestine via unknown transport system. In a heterologous expression system using Xenopus oocytes, sodium-coupled monocarboxylate transporter 1 (SMCT1) has been reported to accept 5-ASA as a substrate. Although SMCT1 is found to be expressed in the large intestine, it is unknown whether SMCT1 is responsible for 5-ASA absorption from the large intestine or not. Here we determined the transport characteristics of 5-ASA in the isolated everted sac prepared from mouse large intestine. Na⁺-dependent uptake of [³H]nicotinate, a substrate for SMCT1, in mouse colon was competitively inhibited by 5-ASA with IC₅₀ value of 2.8 mM. In addition to nicotinate, 5-ASA uptake in mouse colonic mucosa was Na⁺-dependent and saturable with Michaelis constant (K_m) of 2.4 mM. Na⁺-activation kinetics revealed that the Na⁺-to-5-ASA stoichiometry was 2:1 and concentration of Na⁺ necessary for half-maximal transport (K_0.5^Na) was 36.1 mM. Na⁺-dependent 5-ASA uptake was competitively inhibited by nicotinate with an inhibitory constant (K_i) of 2.1 mM was comparable to the K_m value of Na⁺-dependent nicotinate uptake (0.99 mM). Furthermore, ibuprofen, a selective SMCT1 inhibitor, was found to have a significantly inhibitory effect on the Na⁺-dependent 5-ASA uptake in mouse colon (IC₅₀ = 0.19 mM). Taken collectively, these results indicated that SMCT1 in the mouse colonic mucosa is responsible for Na⁺-dependent 5-ASA uptake.

KEYWORDS: {{ getKeywords(articleDetailText.words) }}