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BRET-based G Protein Biosensors for Measuring G Protein-Coupled Receptor Activity in Live Cells
Published on: November 7, 2025
Distinct expression and ligand-binding profiles of two constitutively active GPR17 splice variants
T Benned-Jensen1, M M Rosenkilde
1Department of Neuroscience and Pharmacology, The Panum Institute, Copenhagen University, Denmark.
British Journal of Pharmacology
|February 13, 2010
Summary
This study characterizes two GPR17 receptor isoforms, revealing distinct expression patterns and ligand-binding profiles. Both isoforms exhibit constitutive activity, suggesting tissue-specific functions for GPR17.
Area of Science:
- Molecular pharmacology
- Receptor biology
- G protein-coupled receptors
Background:
- The G protein-coupled receptor GPR17 exists in two isoforms (short and long) differing in N-terminus length.
- Only the short GPR17 isoform has been previously characterized.
- Investigating both isoforms is crucial for understanding GPR17 function.
Purpose of the Study:
- To characterize gene expression and ligand-binding profiles of both human GPR17 isoforms.
- To uncover and characterize the constitutive activity of both GPR17 splice variants.
- To determine potential tissue-specific functions of GPR17 isoforms.
Main Methods:
- Quantitative RT-PCR to determine expression levels in human tissues (brain, heart, kidney).
- CREB reporter assay and [(35)S]-GTPgammaS binding to assess constitutive activity and ligand activation.
- Homologous competition binding and antibody-feeding experiments for leukotriene binding and internalization studies.
Main Results:
- Short GPR17 isoform (hGPR17-S) is more abundant in the brain; long isoform (hGPR17-L) is more abundant in heart and kidney.
- Uracil nucleotides activate hGPR17-S with micromolar potency; hGPR17-L shows significantly lower potency (50-170 fold increase in EC50).
- Neither isoform binds or is activated by cysteinyl leukotrienes; both exhibit constitutive activity via Galpha(i).
Conclusions:
- This study provides the first isoform-specific characterization of human GPR17.
- Significant differences in expression patterns and pharmacological profiles exist between hGPR17-S and hGPR17-L.
- The distinct characteristics suggest that the two GPR17 isoforms may fulfill tissue-specific roles.
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