Overview

• The University of Oklahoma team reports that the three brain amylin receptors share a calcitonin receptor core paired with distinct RAMP1–3 subunits, creating AMY1R, AMY2R, and AMY3R.
• New biochemical and pharmacological assays reveal that agonists can push subunits apart or pull them together, producing subtype-specific signaling effects.
• In live-cell and solubilized-receptor tests, rat amylin promoted assembly of AMY1R and AMY2R, whereas calcitonin agonists destabilized AMY3R, shaping downstream signaling strength.
• The methods let developers measure exactly how candidate compounds act at each amylin receptor, providing mechanistic guidance for designing more selective, better-tolerated obesity therapies.
• The work, published in Science Signaling (DOI: 10.1126/scisignal.adt8127), is an experimental in vitro advance intended to inform ongoing industry programs and will require in vivo validation.