Table 1.
G protein-coupled receptor physiology and pathology in pulmonary hypertension
| Physiology | Ligand-receptor-reference | Cell | G-protein | Important pathways | PH pathology |
|---|---|---|---|---|---|
| Vasodilation | Adenosine-A2A-AR; PGI2-IP[110–112] | VSMC | Gs | PKA | + |
| EC-eNOS-NO dependent vasodilation | Adenosine-A2A-AR; ApelinAPJ; Relaxin-RXFP; Opioid-KOR[50,51,66,110–112,178,179,182,245,246] | EC | Gi | PKG | + |
| Vasoconstriction | ET1/ETA; Ang II-AT1; TXA2-TP; PAF/ PAFR; Shingosine-1-P/S1P1–5; Ca2+-CaSR[12,21,42,47,54–56,58,69,249,250] | VSMC | Gq/Gi | Ca2+ | − |
| Anti-inflammatory | Adenosine-A2A-AR; PGI2-IP[110] | VSMC | Gs | PKA | + |
| PGI2-IP; adenosine-A2AAR[232,239] | Macrophage | Gs | PKA | + | |
| PGI2-IP; adenosine-A2AAR[110] | Fibroblast | Gs | PKA | + | |
| PGI2-IP; Adenosine-A2A-AR[110] | EC | Gs | PKA | + | |
| Pro-inflammatory | ET1-ETA; MCP1-CCR2; RANTES-CCR5; TXA2-TP[69,163] | VSMC | Gq/Gi | Ca2+ | − |
| LTB4-LTB4R; MCP1-CCR2[163,164] | Macrophage | Gq/Gi | Ca2+ | − | |
| PAF-PAFR; TXA2-TP[46,167,169] | EC | Gq/Gi | Ca2+ | − | |
| Cardiac myocyte hypertrophy | AngII-AT1; succinate-GPR91; thrombin-PAR[205,206] | Cardiac myocyte | Gq/Gi | Ca2+ | − |
| Cardiac fibrosis | Thrombin-PAR1–4[223,225] | Cardiac fibroblast | Gq/Gi/G12/13 | Ca2+/RhoA | − |
+: PH-protective; −: PH-pathogenic; VSMC: vascular smooth muscle cells; EC: endothelial cell