Proposed therapeutic applications of functional selectivity and biased signaling
| Receptor | Effect | Therapy | Ref. |
|---|---|---|---|
| Thyroid-stimulating hormone | Activation Gaq>>Gαs | Selective thyroid hormone synthesis | Vassart and Dumont (1992) |
| β-Adrenoceptor | Activation Gas>>Gα1 | Treatment of congestive heart failure | Shizudu and Buttrick (2002) |
| Histamine | ↑cAMP >>allergic response | Neuropsychiatric/neurodegenerative disorders | Galeotti et al. (2004) |
| GPR109 | Gαi >> β-arrestin activation | ↓ Triglycerides with no cutaneous flushing | Walters et al. (2009); Richman et al. (2008) |
| α2-Adrenoceptor | ↓ β-Arrestin activation | Hypotension with reduced sedation | Schmid and Bohn (2009) |
| Dopamine D2 | ↓ Mitogen-activated protein kinase phosphorylation + ↓ internalization | Improved profile for treatment of schizophrenia | Grady et al. (2003); Urban et al. (2007) |
| PTH | Selective β-arrestin activation | Improved treatment of osteoporosis | Gesty-Palmer et al. (2009); Schmid et al. (2008) |
| Opioid | ↓ β-Arrestin interaction | Analgesia with ↓tolerance/↓respiratory depression/↓constipation | Xu et al. (2007); Bohn et al. (1999); Groer et al. (2007) |
| Dopamine D1 | ↓ Internalization | Improved therapy for Parkinson | Ryman-Rasmussen et al. (2007) |
| Angiotensin | ↑ β-Arrestin activation/↓ G protein activation | Antihypertensive therapy with antiapoptitic effect | Wei et al. (2003); Rajagopla et al. (2005); Violin and Lefkowitz (2007) |
| Angiotensin | ↑ β-Arrestin activation/↓ G protein activation | Antihypertensive effect with cardioprotection | Zhai et al. (2005); Rajagopal et al. (2006); Aplin et al. (2009) |
| 5-Hydroxytryptamine | ↓ Interaction with PTEN | Treatment of addiction | Ji et al. (2006) |
| Gastrin-releasing peptide/Arg vasopressin | Receptor blockade + ERK stimulation | Treatment of small-cell lung cancer | MacKinnon et al. (2005) |
| β-Adrenoceptor | Receptor blockade + ERK stimulation | Improved treatment of congestive heart failure | Metra et al. (2004); Wisler et al. (2007) |
| Many overexpressed seven-transmembrane receptors | ↑ Receptor internalization | Numerous cancers | Bosier and Hermans (2007) |
| 5-Hydroxytryptamine | ↑ Receptor internalization | Treatment of psychosis/depression | Willins et al. (1999) |