This longitudinal mechanistic physiological study examines biased β2-adrenergic receptor (β2-AR) signaling in human skeletal muscle, with emphasis on G protein-coupled receptor kinase (GRK)-mediated pathways. Participants will receive daily oral dosing of the GRK-selective long-acting β2-agonist ATR-258 for 8 weeks. Muscle biopsies and physiological measurements will quantify GRK-, cAMP/PKA-, and β-arrestin-related signaling, fiber-type specificity, and potential receptor desensitization with repeated stimulation.
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Intensity of β2-AR downstream signaling pathways (GRK, cAMP/PKA, and β-arrestin) in type I and type II muscle fibers
Timeframe: Before and 4 hours after ATR-258 ingestion on day 1, 29, and 56.