Reason for ARIP’s differential efficacy on ß-arrestin isoforms

Investigate the reason for the observed differences in ARIP’s inhibitory effects on ß-arrestin 1 versus ß-arrestin 2, particularly in class B G protein–coupled receptors characterized by high arrestin-complex stability.

Background

Across the receptor panel, ARIP often exhibited stronger inhibition of ß-arrestin 2 than ß-arrestin 1, despite high sequence conservation in the N-domain groove where V2Rpp binds.

The authors discuss potential explanations (e.g., receptor-specific differential affinities for the arrestin isoforms) but note these do not account for all observations, such as at V2R, leaving the cause of the isoform-specific effects unresolved.