G protein-coupled receptor expression and function in pulmonary artery smooth muscle cells: new targets in pulmonary arterial hypertension

Daniel McDonald, Nakon Aroonsakool, Ohmin Kwon, Paul Insel, Fiona Murray

Research output: Contribution to journalAbstract

Abstract

Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance, in part due to increased proliferation of pulmonary artery smooth muscle cells (PASMC). Since 3’5’-cyclic adenosine monophosphate (cAMP) decreases proliferation of PASMC, G protein-coupled receptors (GPCRs) that couple to Gαs or Gαi are attractive targets for the treatment of PAH. We used a real-time PCR GPCR array to identify and quantify the GPCRs expressed by PASMC isolated from normal subjects and from patients with PAH. We found that human PASMC express >135 GPCRs, at least 60 of which regulate cAMP formation. GPCR expression correlates with function: for Gαs-coupled GPCRs with formation of cAMP and inhibition of cell proliferation, thus documenting that the GPCR array identifies physiologically relevant GPCRs. PAH-PASMC (both from idiopathic and secondary PAH patients) have an increase (>2-fold) in the expression of 41 GPCRs compared to control-PASMC, including multiple GPCRs that link to Gαs or Gαi. In addition, PAH-PASMC have a higher expression of GPCRs that preferentially couple to Gαq/11 or to Gα12/13. Taken together these data provide evidence that a GPCRomic approach can identify GPCRs that may contribute to the physiology of PASMC and that may be new druggable targets for PAH, a disease for which no currently optimal therapies exist.
Original languageEnglish
Article number1090.3
Number of pages1
JournalThe FASEB Journal
Volume28
Issue numberSuppl 1
Publication statusPublished - Apr 2014

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