Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2.
Article Details
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Terada T, Sawada K, Saito H, Hashimoto Y, Inui K
Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2.
Eur J Pharmacol. 2000 Mar 24;392(1-2):11-7.
- PubMed ID
- 10748266 [ View in PubMed]
- Abstract
The novel oral hypoglycemic agent nateglinide (AY4166) is a nonsulfonylurea insulin secretagogue, and its pharmacokinetic features include rapid absorption and elimination. As nateglinide is a dipeptide-like drug, we investigated the interaction of nateglinide with peptide transporters PEPT1 and PEPT2, which mediate the absorption of various peptide-like drugs. Nateglinide exhibited a potent inhibitory effect on [14C]glycylsarcosine uptake by the human colon adenocarcinoma cell line Caco-2 and rat PEPT-transfectants. Kinetic analysis revealed that these inhibitory effects were noncompetitive. Na(+)-coupled alanine or threonine uptake by Caco-2 cells was not inhibited by nateglinide, suggesting that the inhibitory effect of nateglinide on peptide transporters was not due to nonspecific interaction. There was little uptake of [14C]nateglinide by peptide transporters. Various sulfonylureas, such as glibenclamide, also inhibited [14C]glycylsarcosine uptake by rat PEPT-transfectants. In conclusion, nateglinide as well as sulfonylureas inhibit the transport activity of PEPT1 and PEPT2, although nateglinide itself is not transported by these transporters.
DrugBank Data that Cites this Article
- Drug Transporters
Drug Transporter Kind Organism Pharmacological Action Actions Chlorpropamide Solute carrier family 15 member 1 Protein Humans UnknownInhibitorDetails Chlorpropamide Solute carrier family 15 member 2 Protein Humans UnknownInhibitorDetails Nateglinide Solute carrier family 15 member 1 Protein Humans UnknownInhibitorDetails Nateglinide Solute carrier family 15 member 2 Protein Humans UnknownInhibitorDetails Tolbutamide Solute carrier family 15 member 1 Protein Humans UnknownInhibitorDetails Tolbutamide Solute carrier family 15 member 2 Protein Humans UnknownInhibitorDetails