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Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons
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Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons
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Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons
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Journal Article
Specific pharmacological and Gi/o protein responses of some native GPCRs in neurons
2024
Overview
G protein-coupled receptors (GPCRs) constitute the largest family of membrane proteins and are important drug targets. The discovery of drugs targeting these receptors and their G protein signaling properties are based on assays mainly performed with modified receptors expressed in heterologous cells. However, GPCR responses may differ in their native environment. Here, by using highly sensitive G
i/o
sensors, we reveal specific properties of G
i/o
protein-mediated responses triggered by GABA
B
, α
2
adrenergic and cannabinoid CB1 receptors in primary neurons, different from those in heterologous cells. These include different profiles in the G
i/o
protein subtypes-mediated responses, and differences in the potencies of some ligands even at similar receptor expression levels. Altogether, our results show the importance of using biosensors compatible with primary cells for evaluating the activities of endogenous GPCRs in their native environment.
G protein responses mediated by GPCRs may differ depending on their environment. Here, using highly sensitive Gi/o sensors, the authors reveal the specific pharmacological and Gi/o protein responses of some native GPCRs in neurons, and the influence of G protein composition.
