Abstract:
:While the physiological function and mechanisms of agonist-dependent G protein-coupled receptor (GPCR) internalization have been extensively studied, the functional characterization of constitutive internalization of these critically important receptors has received less attention. Here we relate the constitutive internalization of more than 30 therapeutically targeted GPCRs to their agonist-induced internalization. The constitutive internalization ranges from levels of bulk membrane endocytosis in some cases to levels of agonist-induced internalization for other receptors. Moreover, for receptors with high constitutive internalization this occludes further agonist-induced internalization. Additionally, Gq-coupled GPCRs show a significantly higher rate of constitutive internalization than Gs- and Gi-coupled receptors. Finally, we consolidate the proposed link between the constitutive internalization, as assessed by a cytometry-based assay, and the constitutive activity of these receptors, as previously reported by a β-arrestin recruitment assay across the range of pharmacologically relevant receptors. In summary, we provide a quantitative comparison of GPCR internalization across a range of pharmacologically relevant receptors providing generalized insight into the relations between constitutive internalization, constitutive activity and agonist-induced internalization, which has so far relied on mutational studies in individual receptors.
journal_name
Basic Clin Pharmacol Toxicoljournal_title
Basic & clinical pharmacology & toxicologyauthors
Hendrik Schmidt J,Perslev M,Bukowski L,Stoklund M,Herborg F,Herlo R,Lindegaard Madsen Kdoi
10.1111/bcpt.13274subject
Has Abstractpub_date
2020-06-01 00:00:00pages
116-121eissn
1742-7835issn
1742-7843journal_volume
126 Suppl 6pub_type
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