Prolonged exposure of a cell to high concentrations of a beta-adrenergic agonist leads to progressive loss of responsiveness despite continued presence of the ligand. Which molecular event best explains this desensitization?

• A GRK-mediated phosphorylation of the receptor followed by beta-arrestin binding ✓
• B Covalent ADP-ribosylation of the alpha subunit of Gs
• C Proteolytic degradation of adenylyl cyclase
• D Hydrolysis of GTP bound to the alpha subunit by cholera toxin-like activity

Explanation

With sustained agonist exposure, G protein-coupled receptor kinases (GRKs) phosphorylate the occupied receptor, creating a docking site for beta-arrestin. Beta-arrestin sterically blocks further Gs coupling and targets the receptor for internalization, producing homologous desensitization. Option B describes cholera toxin action, which actually increases signalling rather than reducing it, so it cannot explain loss of responsiveness.

Reference: Ganong's Review of Medical Physiology, 26th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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