biostudies-literatureUnknown14(1)Mickols EUppsala University3D spheroids of primary human hepatocytes (3D PHH) retain a differentiated phenotype with largely conserved metabolic function and proteomic fingerprint over weeks in culture. As a result, 3D PHH are gaining importance as a model for mechanistic liver homeostasis studies and in vitro to in vivo extrapolation (IVIVE) in drug discovery. However, the kinetics and regulation of drug transporters have not yet been assessed in 3D PHH. Here, we used organic cation transporter 1 (OCT1/SLC22A1) as a model to study both transport kinetics and the long-term regulation of transporter activity via relevant signalling pathways. The kinetics of the OCT1 transporter was studied using the fluorescent model substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) and known OCT1 inhibitors in individuScientific reports17334https://www.ebi.ac.uk/biostudies/studies/S-EPMC11283471biostudies-literatureOCT1 (SLC22A1) transporter kinetics and regulation in primary human hepatocyte 3D spheroids.PMC11283471Stuwe MArtursson PKarlgren MBlom KMickols EEriksson JHandin NSellin MELauschke VMMeyer ARudfeldt JFryknas MfalseOCT1 (SLC22A1) transporter kinetics and regulation in primary human hepatocyte 3D spheroids.3D spheroids of primary human hepatocytes (3D PHH) retain a differentiated phenotype with largely conserved metabolic function and proteomic fingerprint over weeks in culture. As a result, 3D PHH are gaining importance as a model for mechanistic liver homeostasis studies and in vitro to in vivo extrapolation (IVIVE) in drug discovery. However, the kinetics and regulation of drug transporters have not yet been assessed in 3D PHH. Here, we used organic cation transporter 1 (OCT1/SLC22A1) as a model to study both transport kinetics and the long-term regulation of transporter activity via relevant signalling pathways. The kinetics of the OCT1 transporter was studied using the fluorescent model substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) and known OCT1 inhibitors in individu2024-01-01T00:00:00Z2024 Jul2026-06-02T22:59:18.796Z2026-04-21T03:14:08.447ZS-EPMC112834713906819810.1038/s41598-024-67192-6