Work

Evidence for effective suppression of INa and IK(DR) by AS2034178 (bis{2-[(4-{(4′-(2-hydroxyethoxy)-2′-methyl[1,1′-biphenyl]-3-yl)methoxy}phenyl]methyl]-3,5-dioxo-1,2,4-oxadiazolidin-4-ide} tetrahydrate), an agonist of free fatty acid receptor

Year: 2025

Type: article

Abstract: AS2034178, an agonist of free fatty acid receptor-1 or G protein-coupled receptor 40, enhances pancreatic β-cell function. Its impact on ionic currents in excitable cells, particularly pituitary tumor (GH 3 ) cells, was investigated. AS2034178 suppressed transient ( I Na(T) ) and late ( I Na(L) ) components of voltage-gated Na + current ( I Na ) with IC 50 values of 29.8 and 5.3 µM, respectively. It did not alter current–voltage relationship but shifted steady-state inactivation curve of I Na(T) leftward. AS2034178 also blocked persistent Na + current ( I Na(P) ) activated by long-lasting ramp voltages, and subsequent application of deltamethrin or tefluthrin attenuated its suppression. The compound prolonged recovery of I Na(P) inactivation, shifted its inactivation curve, and shortened time constant for I N(P) decay. Additionally, AS2034178 suppressed delayed-rectifier K + current ( I K(DR) ) with a dissociation constant of 6.23 µM. Docking studies suggested AS2034178′s ability to interact with amino acid residues in hNa V 1.7 channels.(supplementary data). AS2034178′s effects on ionic currents ( I Na and I K(DR) ) contribute to its mechanisms of action in culture or in vivo .

Source: Neuroscience Letters

DOI: 10.1016/j.neulet.2025.138222