Signalling in response to sub-picomolar concentrations of active compounds: Pushing the boundaries of GPCR sensitivity

British Journal of Pharmacology
Srgjan Civciristov, Michelle L Halls

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 β2 -adrenoceptor; and the M3 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. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wil...Continue Reading

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Citations

Jun 27, 2019·British Journal of Pharmacology·Martin C MichelRoger J Summers
Apr 3, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Yunjun GeRichard D Ye
Aug 10, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Shuo ZhangRichard D Ye
Jun 23, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Edward J Calabrese, James Giordano

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