Dopamine Receptor D1 Agonism and Antagonism Using a Field-Effect Transistor Assay

Seon Joo Park, Heehong Yang, Seung Hwan Lee, Hyun Seok Song, Chul Soon Park, Joonwon Bae, Oh Seok Kwon, Tai Hyun Park, Jyongsik Jang

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

The field-effect transistor (FET) has been used in the development of diagnostic tools for several decades, leading to high-performance biosensors. Therefore, the FET platform can provide the foundation for the next generation of analytical methods. A major role of G-protein-coupled receptors (GPCRs) is in the transfer of external signals into the cell and promoting human body functions; thus, their principle application is in the screening of new drugs. The research community uses efficient systems to screen potential GPCR drugs; nevertheless, the need to develop GPCR-conjugated analytical devices remains for next-generation new drug screening. In this study, we proposed an approach for studying receptor agonism and antagonism by combining the roles of FETs and GPCRs in a dopamine receptor D1 (DRD1)-conjugated FET system, which is a suitable substitute for conventional cell-based receptor assays. DRD1 was reconstituted and purified to mimic native binding pockets that have highly discriminative interactions with DRD1 agonists/antagonists. The real-time responses from the DRD1-nanohybrid FET were highly sensitive and selective for dopamine agonists/antagonists, and their maximal response levels were clearly different depending on their DRD1 affinities. Moreover, the equilibrium constants (K) were estimated by fitting the response levels. Each K value indicates the variation in the affinity between DRD1 and the agonists/antagonists; a greater K value corresponds to a stronger DRD1 affinity in agonism, whereas a lower K value in antagonism indicates a stronger dopamine-blocking effect.

Original languageEnglish
Pages (from-to)5950-5959
Number of pages10
JournalACS Nano
Volume11
Issue number6
DOIs
StatePublished - 27 Jun 2017

Bibliographical note

Publisher Copyright:
© 2017 American Chemical Society.

Keywords

  • agonism-antagonism
  • agonists-antagonists
  • dopamine
  • dopamine receptor D1
  • equilibrium constants
  • field-effect transistor
  • nanohybrids

Fingerprint

Dive into the research topics of 'Dopamine Receptor D1 Agonism and Antagonism Using a Field-Effect Transistor Assay'. Together they form a unique fingerprint.

Cite this