Signalling in response to sub-picomolar concentrations of active compounds

Pushing the boundaries of GPCR sensitivity

Research output: Contribution to journalReview ArticleResearchpeer-review

1 Citation (Scopus)

Abstract

There is evidence for ultra-sensitive responses to active compounds at concentrations below picomolar levels by proteins and receptors found in species ranging from bacteria to mammals. We have recently shown that such ultra-sensitivity is also demonstrated by a wide range of prototypical GPCRs, and we have determined the molecular mechanisms behind these responses for three family A GPCRs: the relaxin receptor, RXFP1; the β 2 -adrenoceptor; and the M 3 muscarinic ACh receptor. Interestingly, there are reports of similar ultra-sensitivity by more than 15 human GPCR families, in addition to other human receptors and channels. These occur through a diverse range of signalling pathways and produce modulation of important physiological processes, including neuronal transmission, chemotaxis, gene transcription, protein/ion uptake and secretion, muscle contraction and relaxation, and phagocytosis. Here, we summarise the accumulating evidence of ultra-sensitive receptor signalling to show that this is a common, though currently underappreciated, property of GPCRs.

Original languageEnglish
Pages (from-to)2382-2401
Number of pages20
JournalBritish Journal of Pharmacology
Volume176
Issue number14
DOIs
Publication statusPublished - Jul 2019

Cite this

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title = "Signalling in response to sub-picomolar concentrations of active compounds: Pushing the boundaries of GPCR sensitivity",
abstract = "There is evidence for ultra-sensitive responses to active compounds at concentrations below picomolar levels by proteins and receptors found in species ranging from bacteria to mammals. We have recently shown that such ultra-sensitivity is also demonstrated by a wide range of prototypical GPCRs, and we have determined the molecular mechanisms behind these responses for three family A GPCRs: the relaxin receptor, RXFP1; the β 2 -adrenoceptor; and the M 3 muscarinic ACh receptor. Interestingly, there are reports of similar ultra-sensitivity by more than 15 human GPCR families, in addition to other human receptors and channels. These occur through a diverse range of signalling pathways and produce modulation of important physiological processes, including neuronal transmission, chemotaxis, gene transcription, protein/ion uptake and secretion, muscle contraction and relaxation, and phagocytosis. Here, we summarise the accumulating evidence of ultra-sensitive receptor signalling to show that this is a common, though currently underappreciated, property of GPCRs.",
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Signalling in response to sub-picomolar concentrations of active compounds : Pushing the boundaries of GPCR sensitivity. / Civciristov, Srgjan; Halls, Michelle L.

In: British Journal of Pharmacology, Vol. 176, No. 14, 07.2019, p. 2382-2401.

Research output: Contribution to journalReview ArticleResearchpeer-review

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