Abstract:
:In recent years, special attention has been paid to the A3 adenosine receptor (A3AR) as a possible pharmacological target to treat intestinal inflammation. In this work, it was set up a novel method to quantify the concentration of a promising anti-inflammatory agent inside and outside of intestinal barrier using the everted gut sac technique. The compound chosen for the present study is one of the most potent and selective A3AR agonist reported so far, named AR 170 (N6-methyl-2-phenylethynyl-5'-N-methylcarboxamidoadenosine). In order to evaluate the intestinal absorption of AR 170 the radioligand binding assay in comparison with HPLC-DAD was used. Results showed that the compound is absorbed via passive diffusion by paracellular pathway. The concentrations determined in the serosal (inside the sac) fluid by radioligand binding assay are in good agreement with those obtained through the widely used HPLC/MS protocol, demonstrating the reliability of the method. It is worthwhile to note that the radioligand binding assay allows detecting very low concentrations of analyte, thus offering an excellent tool to measure the intestinal absorption of receptor ligands. Moreover, the AR 170 quantity outside the gut sac and the interaction with A3AR could presuppose good topical anti-inflammatory effects of this compound.
journal_name
Bioorg Med Chemjournal_title
Bioorganic & medicinal chemistryauthors
Buccioni M,Dal Ben D,Lambertucci C,Martí Navia A,Ricciutelli M,Spinaci A,Volpini R,Marucci Gdoi
10.1016/j.bmc.2019.06.011subject
Has Abstractpub_date
2019-08-01 00:00:00pages
3328-3333issue
15eissn
0968-0896issn
1464-3391pii
S0968-0896(19)30653-4journal_volume
27pub_type
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