Study identifies phenylacetylglutamine (PAGln), a gut microbiome metabolite, as a novel allosteric modulator of β2-adrenergic receptors, offering insights into its role in cardiovascular disease (CVD) risk.
By Hugo Francisco de SouzaReviewed by Benedette Cuffari, M.Sc.Aug 26 2024 Study: Gut microbe-generated phenylacetylglutamine is an endogenous allosteric modulator of β2-adrenergic receptors. Image Credit: Explode / Shutterstock.com
As research advances, the relationship between diet, gut microbiota, and public health is becoming increasingly evident. A growing body of literature highlights the association between gut microbial assemblages and psychological outcomes, including obesity, diabetes, and CVD risk. About the study Previous studies have identified the adrenergic receptor -binding potential of PAGln, which suggests its potential role in allosteric modulation. ARs are host receptors involved in a wide range of critical metabolic, homeostatic, and cardiovascular functions across the heart, adipose tissue, neurons, and vasculature. The present study aims to verify this hypothesis and further identify the regulatory 'fine-tuning' pathways linking PAGln to CVD outcomes.
To non-invasively monitor the dynamic allosteric modulation of ARs following PAGln treatment, dynamic mass redistribution studies on mutant β2-HEK293 cells were performed. To determine whether these interactions occur under normal physiological conditions, the β-arrestin2 recruitment assay was used to assess the effects of PAGln as a negative allosteric modulator with or without prior exposure to β-agonists. Exposure to PAGln for 15 minutes or longer, followed by treatment with β-agonists for 10 minutes, led to similar results obtained during the cAMP assay, thus indicating that PAGln elicits NAM effects in β2AR- but not β1AR-expressing HEK293 cells.
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