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Identification of G protein‐coupled receptor (GPCR) targets in pulmonary artery smooth muscle cells
Author(s) -
Aroonsakool Nakon,
Kwon Ohmin,
Insel Paul A,
Murray Fiona
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1020.8
Subject(s) - g protein coupled receptor , receptor , biology , microbiology and biotechnology , gq alpha subunit , intracellular , pulmonary artery , neuropeptide , signal transduction , second messenger system , medicine , endocrinology , biochemistry
The second messenger cAMP is an important regulator of vascular tone and cellular proliferation in the pulmonary artery (PA). Decreased intracellular levels of cAMP in pulmonary artery smooth muscle cells (PASMC) contribute to the abnormal tone and remodeling in the PA that characterizes diseases such as pulmonary arterial hypertension. G‐protein coupled receptors (GPCRs) that couple to Gα s or Gα i , are attractive drug targets to increase cAMP in PASMC. We used a TaqMan® GPCR array to identify novel pulmonary specific GPCRs that could regulate cAMP‐dependent signaling in human PASMC. We found that PASMC express 88 GPCRs, the most abundant of which were orphan receptors. Using real‐time PCR, antibodies and specific agonists and antagonists we validated the most abundant Gα s ‐ and Gα i ‐coupled GPCRs. Initial efforts focused on the vasoactive intestinal peptide receptor 1 (VIPR1), one of the highest expressed Gα s ‐coupled GPCRs in PASMC. We found that VIPR1 protein is expressed on the plasma membrane of PASMC, activation of which by VIP (1 μM, 10 min) significantly increased cAMP accumulation. These data demonstrate quantitative mRNA expression of GPCRs in PASMC and evidence that such an approach can identify previously unrecognized GPCRs that contribute to physiology and pathophysiology in the pulmonary vasculature. Supported by NIH