Uncovering the pharmacology of GPR75: role in pulmonary arterial hypertension

Year of award: 2016


  • Dr Fiona Murray

    University of Aberdeen

Project summary

Pulmonary arterial hypertension (PAH) is a devastating condition that if left untreated will leave the patient with an average life expectancy of less than three years from diagnosis. PAH is associated with proliferation of pulmonary artery smooth muscle cells (PASMC), which contributes to increased vascular resistance. The maintenance of the low vascular tone in the pulmonary circulation is dependent on the interaction of circulating and locally produced mediators, many of which act via G protein-coupled receptors (GPCRs). The accessibility of GPCRs on the plasma membrane, their tissue-selective distribution and role in regulating physiological functions make them excellent pharmacological targets.

We used an unbiased approach (GPCR real-time-PCR arrays) to profile GPCR expression in PASMC isolated from controls and patients with PAH. Our data revealed that PAH-PASMC uniquely express an orphan GPCR (whose endogenous ligand has not yet been identified) compared with control-PASMC, namely GPR75. We aim to validate GPR75 as a novel target for PAH by uncovering its pharmacology and the functional significance and expression of receptor variants in PAH and by elucidating its physiological role in vivo.

Our hypothesis is that GPR75 is a key regulator of PASMC proliferation that characterises PAH and this will be a new target or genetic risk factor for the disease.