Dynamic mass redistribution assays decode surface influence on signaling of endogenous purinergic P2Y receptors

Assay Drug Dev Technol. 2012 Feb;10(1):37-45. doi: 10.1089/adt.2011.0392. Epub 2011 Nov 8.

Abstract

Interactions with extracellular matrices (ECM) shape the signaling and functions of many types of cells and receptors, and distinct ECM coatings have been used in a wide range of substrates for drug discovery processes. Here, we investigate the influence of ECM protein coatings on the signaling of endogenous purinergic 2Y (P2Y) receptors in human embryonic kidney HEK293 cells using dynamic mass redistribution (DMR) assays enabled by label-free optical biosensor. Results showed that ECM proteins had significant impacts on the DMR characteristics, potency, and efficacy of seven P2Y agonists. This study documents the importance of surface chemistry in regulating receptor signaling.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Diphosphate / analogs & derivatives
  • Adenosine Diphosphate / metabolism
  • Adenosine Diphosphate / pharmacology
  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Biosensing Techniques / methods*
  • Dose-Response Relationship, Drug
  • Extracellular Matrix / drug effects
  • Extracellular Matrix / metabolism
  • HEK293 Cells
  • Humans
  • Purinergic P2Y Receptor Agonists / metabolism
  • Purinergic P2Y Receptor Agonists / pharmacology
  • Purinergic P2Y Receptor Antagonists / metabolism
  • Purinergic P2Y Receptor Antagonists / pharmacology
  • Receptors, Purinergic P2Y / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / physiology*
  • Surface Properties / drug effects
  • Uridine Diphosphate / metabolism
  • Uridine Diphosphate / pharmacology

Substances

  • N(6)-methyl-2'-deoxyadenosine 3',5'-diphosphate
  • Purinergic P2Y Receptor Agonists
  • Purinergic P2Y Receptor Antagonists
  • Receptors, Purinergic P2Y
  • Uridine Diphosphate
  • Adenosine Diphosphate
  • Adenosine Triphosphate