The signaling and selectivity of α-adrenoceptor agonists for the human α2A, α2B and α2C-adrenoceptors and comparison with human α1 and β-adrenoceptors.

ABSTRACT: α2-adrenoceptors, (α2A, α2B and α2C-subtypes), are Gi-coupled receptors. Central activation of brain α2A and α2C-adrenoceptors is the main site for α2-agonist mediated clinical responses in hypertension, ADHD, muscle spasm and ITU management of sedation, reduction in opiate requirements, nausea and delirium. However, despite having the same Gi-potency in functional assays, some α2-agonists also stimulate Gs-responses whilst others do not. This was investigated. Agonist responses to 49 different α-agonists were studied (CRE-gene transcription, cAMP, ERK1/2-phosphorylation and binding affinity) in CHO cells stably expressing the human α2A, α2B or α2C-adrenoceptor, enabling ligand intrinsic efficacy to be determined (binding K_D /Gi-IC₅₀ ). Ligands with high intrinsic eff

SUBMITTER: Proudman RGW 

PROVIDER: S-EPMC9471048 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature