Abstract:
: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 (Km) 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 (K0.5Na) was 36.1 mM. Na+-dependent 5-ASA uptake was competitively inhibited by nicotinate with an inhibitory constant (Ki) of 2.1 mM was comparable to the Km 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.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Yuri T,Kono Y,Fujita Tdoi
10.1016/j.bbrc.2020.01.139subject
Has Abstractpub_date
2020-04-09 00:00:00pages
561-566issue
3eissn
0006-291Xissn
1090-2104pii
S0006-291X(20)30222-9journal_volume
524pub_type
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