Temporal complexity of LVV-hemorphin-7 allosterism at the angiotensin II type 1 receptor assessed using entropy-based...

Allosteric modulation constitutes an interesting aspect of the molecular pharmacology of hormone receptors and enzymes with implications in basic research and drug discovery. The modulation of the angiotensin II type 1 receptor by the endogenous peptide, LVV-hemorphin 7 (LVV-H7), is an example that was recently reported using various in vitro pharmacological and biochemical approaches as well as in silico analysis. In this study, we used real-time biosensor data using BRET technology and applied sample entropy and multiscale Rényi entropy to measure the effect of LVV-H7 on receptor activity over time. LVV-H7 increased signaling complexity when used alone and stabilized receptor activity when combined with angiotensin II. These effects were different for the Gαq and β-arrestin signaling pathways. The results indicate that LVV-H7 functions to fine-tunes receptor behavior in a dynamic and pathway-specific manner. This highlights the value of entropy-based tools for tracking changes in cell signaling and further exploring hormone receptor pharmacology and signaling with potential applications in drug design and analysis. The study also suggests that endogenous peptides such as LVV-H7 could offer new ways to modulate the angiotensin II receptor for therapeutic benefit.