Selected GPCRs that function through Gq and/or Gs pathways
Their agonists were reported with EC50 value.
| GPCR | Signaling | Functions | Agonists | EC50 or Kd |
|---|---|---|---|---|
| GPER1 (Gpr30) | Gq | Activated by estradiol and functions via Gq signaling (Revankar et al., 2005). A selective agonist G1 is beneficial in myocardial ischemia reperfusion injury model (Bologa et al., 2006; Deschamps and Murphy, 2009). | G1 | 2 nM (Bologa et al., 2006) |
| BDKRB1 | Gq | BDKRB1 is a Gq-coupled GPCR, whereas BDKRB2 signals through Gq and Gi. In vivo activation of BDKRB2 attenuated kidney fibrosis (Schanstra et al., 2002). | Bradykinin | 3.26 nM (Wiernas et al., 1997) |
| DRD1 | Gs | Pleuropulmonary fibrosis was linked to the long-term use of dopamine agonist pergolide in patients with Parkinson (Tintner et al., 2005). | A68930 | 2.5 nM (DeNinno et al., 1991) |
| PTGER2 | Gq | PGE2 is a potent bioactive eicosanoid that strongly inhibits fibroblast proliferation, migration, and collagen secretion (Bozyk and Moore, 2011). | PGE2 | PTGER1, 25 nM; PTGER2, 13 nM; PTGER3, 3 nM; PTGER4, 3 nM (Markovič et al., 2017) |
| PTGER4 | Gs | TCS2510 is a highly selective EP4 agonist. | TCS2510 | 2.5 nM (Billot et al., 2003) |
| TBXA2R | Gq/Gs/G12/13 | U46619 is a potent and stable TBXA2R agonist. | U46619 | 35 nM (Coleman et al., 1981) |
| OXTR | Gq | Oxytocin is a peptide hormone and neurotransmitter signaling through OXTR and Gq pathways (Gimpl and Fahrenholz, 2001). WAY-267464 is a potent, selective, nonpeptide OXTR agonist. | Oxytocin | 9.0–10.8 nM (Gruber et al., 2012) 9.0 nM (Ring et al., 2010) |
| WAY267464 | ||||
| EDNRB | Gq | Endothelin 3 is a vasoconstrictor that preferentially binds to EDNRB. | Endothelin 3 | 1 nM (Sumner et al., 1992) |
| F2RL1 (PAR2) | Gq/Gi | PAR2 is implicated in lung, kidney, liver, and cardiac fibrosis (Palygin et al., 2016; Shearer et al., 2016; Sun et al., 2017; Friebel et al., 2019). | AC264613 | ∼31 nM (Gardell et al., 2008) |
| S1PR3 | Gq | S1PR3 KO mice has attenuated inflammation and fibrosis upon bleomycin-induced lung injury (Murakami et al., 2014). | CYM5541 | 72–132 nM (Jo et al., 2012) |
| HTR2B (5-HT2B receptor) | Gq | Serotonin fibrosis in human and treatment of fenfluramine, a serotonin releasing agent, causes cardiac valve fibrosis in patients with obesity (Roth, 2007). 5-HT2B activation mediates valvular fibroblasts activation. | BW723C86 | 5-HT2B, 1.1 nM; 5-HT2C, 93.3 nM (Porter et al., 1999) |
| HTR7 (5-HT7 receptor) | Gs | AS-19 is a potent 5-HT7 receptor agonist. | AS19 | 0.83 nM (Perez-Garcia and Meneses, 2005) |
| MC1R | Gs | MC1R is anti-inflammatory and has been implicated in several inflammatory diseases. | BMS470539 | 16.8 nM (Kang et al., 2006) |
EDNRB, endothelin receptor B; KO, knockout.