Inhibitory effect of novel oral hypoglycemic agent nateglinide (AY4166) on peptide transporters PEPT1 and PEPT2.

Article Details

Citation

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
DrugTransporterKindOrganismPharmacological ActionActions
ChlorpropamideSolute carrier family 15 member 1ProteinHumans
Unknown
Inhibitor
Details
ChlorpropamideSolute carrier family 15 member 2ProteinHumans
Unknown
Inhibitor
Details
NateglinideSolute carrier family 15 member 1ProteinHumans
Unknown
Inhibitor
Details
NateglinideSolute carrier family 15 member 2ProteinHumans
Unknown
Inhibitor
Details
TolbutamideSolute carrier family 15 member 1ProteinHumans
Unknown
Inhibitor
Details
TolbutamideSolute carrier family 15 member 2ProteinHumans
Unknown
Inhibitor
Details