This article and associated images are based on a poster originally authored by Ravinder K. Bhardwaj, Eline Koers, Alexander Krull, David Sykes, Dmitry Veprintsev and Neil V. Morgan and presented at ELRIG Drug Discovery 2025 in affiliation with University of Birmingham and University of Nottingham.
This poster is being hosted on this website in its raw form, without modifications. It has not undergone peer review but has been reviewed to meet AZoNetwork's editorial quality standards. The information contained is for informational purposes only and should not be considered validated by independent peer assessment.
IP receptor physiologically contributes to the prevention of Cardiovascular events
Image Credit: Image courtesy of Ravinder K. Bhardwaj et al., in partnership with ELRIG (UK) Ltd.
Why investigate IP receptors?
- Prostaglandin I2 is an endogenously produced (by blood vessels) ligand for the prostacyclin receptor (IP receptor)
- keeps vessels and platelets in their physiologically required state, that is, dilated and inactive states, respectively (JB Smith, 1981).
- IP receptor is the first and only cell surface receptor on human platelets that prevents platelets from aggregating otherwise may lead to pathological thrombus formation.
- Despite the acknowledgement of their importance in vessels and platelet physiology, the receptor has remained an understudied therapeutic target
- This study has recognised some ultra-rare novel single nucleotide variations (SNVs) in patients with mild bleeding disorders
- Thus, the study aims to develop an assay to investigate the impact of SNVs on receptor binding and interaction with its ligands, receptor folding, structural integrity and signaling
Aims
- To develop an assay to investigate the impact of SNVs on receptor binding and interaction with its ligands, receptor folding, structural integrity and signaling
- To investigate the association of these mutations to abnormal bleeding phenotype observed in patients and explore their role in platelet dysfunction
Methods and experimental setup
Image Credit: Image courtesy of Ravinder K. Bhardwaj et al., in partnership with ELRIG (UK) Ltd.
BRET mechanism in the developed assay
Image Credit: Image courtesy of Ravinder K. Bhardwaj et al., in partnership with ELRIG (UK) Ltd.
Experimental setup (96-well plate-based format)
Image Credit: Image courtesy of Ravinder K. Bhardwaj et al., in partnership with ELRIG (UK) Ltd.
miniGs-recruitment (BRET Assay)
Graphs 1 and 2. SNV in the C-terminal region of the IP receptor seems to be significantly impacting the miniGs recruitment. SNVs in the ELC1 and ICL2 of IP receptor also show reduced recuitment. Image Credit: Image courtesy of Ravinder K. Bhardwaj et al., in partnership with ELRIG (UK) Ltd.
Conclusion
- The IP receptor is functional and is capable of binding to ligand Iloprost
- Receptor is intracellularly capable of forming a complex with miniGsprotein
- Receptor signalling is plasmid transfection amount and Iloprost dose-dependent (n = 3) – data not shown
Future experiments
- Transfect HEK293 cell lines with engineered plasmid and conduct further functional analysis
- Evaluate mutant stability with ThermoBRET or ThermoFRET GPCR assays
- Measure GPCR trafficking to the cell surface (confocal microscopy and AI-driven analysis
- Evaluate ligand binding and signalling properties with TR-FRET and NanoBRET assays
Acknowledgement
- Dr Natalie Poulter
- Dr Steve Thomas
- Natasha Pavey
References
- Watson, S.P. and Harrison, P. (2010). The Vascular Function of Platelets. pp.772–792. https://doi.org/10.1002/9781444323160.ch40.
- Kaye, A.D., et al. (2020). Platelet Dysfunction Diseases and Conditions: Clinical Implications and Considerations. Advances in Therapy, 37(9), pp.3707–3722. https://doi.org/10.1007/s12325-020-01453-4.
- Saboor, M., et al. (2013). Platelet receptors: An instrumental of platelet physiology. Pakistan Journal of Medical Sciences, 29(3). https://doi.org/10.12669/pjms.293.3497.
- Smith, J.B. (2009). PROSTAGLANDINS AND PLATELET AGGREGATION. Acta Medica Scandinavica, 210(S651), pp.91–98. https://doi.org/10.1111/j.0954-6820.1981.tb03638.x.
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Last Updated: Nov 27, 2025