Modulation of constitutive GPCR activity: a way of life?

G-protein coupled receptors (GPCRs) are highly versatile signalling modules and, as such, one of the most important drug targets in many therapeutic areas. In recent years, the view on GPCR activation has been firmly challenged and it is now clear that GPCRs do not always need external ligands to mo...

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Bibliographic Details
Published in:International Congress series 2003-08, Vol.1249, p.131-138
Main Authors: Leurs, Rob, Bakker, Remko A., Casarosa, Paola, Verzijl, Dennis, Timmerman, Henk, Smit, Martine J.
Format: Article
Language:English
Subjects:
Constitutive activity
GPCR
Histamine receptor
Inverse agonism
ORF74
US28
Viral GPCR
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Summary:G-protein coupled receptors (GPCRs) are highly versatile signalling modules and, as such, one of the most important drug targets in many therapeutic areas. In recent years, the view on GPCR activation has been firmly challenged and it is now clear that GPCRs do not always need external ligands to modulate intracellular signal transduction. The histamine H 3 receptor shows a high level of constitutive activity both in vitro and in vivo. Constitutive H 3 receptor activity might be modulated by biological (receptor isoforms) and chemical means (H 3 receptor ligands). Furthermore, we recently found that constitutive activity seems to be a general characteristic of viral GPCRs, suggesting that the concept of constitutive GPCR activity is successfully exploited by a variety of pathogenic herpes viruses (e.g. HCMV and KSHV). As for most GPCRs, also for constitutively active viral GPCRs (endogenous) and synthetic ligands, can be found that shut down agonist-independent signalling, thereby acting as potential new anti-viral therapeutics.
ISSN:0531-5131
1873-6157
DOI:10.1016/S0531-5131(03)00608-3