A pharmaceutical company develops an antagonist that blocks the beta-arrestin recruitment to beta2-adrenergic receptors while leaving G-protein coupling intact. The clinical consequence would be:

• A Loss of receptor desensitisation and internalization, prolonging adrenergic signalling ✓
• B Enhanced receptor downregulation and tolerance to adrenergic agonists
• C Selective blockade of ERK activation downstream of the beta2 receptor
• D Prevention of GRK2-mediated phosphorylation of the receptor

Explanation

Beta-arrestins serve two functions: they sterically uncouple GPCRs from G-proteins (homologous desensitization) and mediate receptor internalization via clathrin-coated pits. Blocking beta-arrestin recruitment would prevent desensitization and internalization, prolonging cAMP signalling from persistent G-protein coupling. Beta-arrestins also mediate ERK activation independently, so blocking them would reduce (not select for) ERK signalling. GRK2-mediated phosphorylation is upstream of beta-arrestin recruitment and would be unaffected by this antagonist.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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