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Cloning the Y2 Receptor From Human Brain — A Major Anti-Obesity Drug Target

RPEP-003211995Gerald, C; Walker, M W; Vaysse, P J; He, C; Branchek, T A; Weinshank, R L
In VitroStrong evidence
The takeaway

The human Y2 receptor was cloned from hippocampus, binding NPY and PYY but not pancreatic polypeptide — a key appetite-regulation target.

Anti-obesity target

Y2 is the receptor through which the gut hormone PYY signals fullness — a natural "stop eating" switch

What the researchers found

The human Y2 receptor was cloned from hippocampus and shown to selectively bind NPY and PYY but not pancreatic polypeptide.

Why it matters

The Y2 receptor is a key regulator of appetite and is the target of PYY(3-36), a gut hormone that reduces food intake. Cloning it enabled development of anti-obesity drug candidates.

How the study worked

Expression cloning from a human hippocampal cDNA library. The receptor was expressed in cells and characterized using radioligand binding and functional assays.

What this study cannot tell us

In vitro characterization of a cloned receptor. Receptor behavior in cell lines may not fully represent its function in brain circuits.

How to read the evidence

Strong — molecular cloning with functional characterization and selectivity profiling.

When this study was published

Published in 1995 (31 years ago). Y2 agonists and PYY analogs are in clinical development for obesity.

The bigger picture

PYY(3-36) acting through Y2 is one of the body's main "stop eating" signals. Cloning this receptor opened a major avenue for anti-obesity drug development.

Questions still open

  • Can Y2-selective drugs mimic the appetite-suppressing effect of PYY?
  • Is Y2 receptor expression altered in obesity?

Common questions

What makes Y2 special for weight loss?
Y2 is the receptor that PYY(3-36) — a gut hormone released after eating — uses to tell the brain "stop eating." Drugs that activate Y2 could mimic this natural fullness signal.
Are there Y2-based obesity drugs?
PYY(3-36) analogs and Y2-selective drugs are in clinical development. This 1995 cloning study was a critical enabling step for that research.

Read the original research

Expression cloning and pharmacological characterization of a human hippocampal neuropeptide Y/peptide YY Y2 receptor subtype.

The Journal of biological chemistry, 270(45), 26758-61

View on PubMed ↗

Citation

Gerald, C; Walker, M W; Vaysse, P J; He, C; Branchek, T A; Weinshank, R L. (1995). Expression cloning and pharmacological characterization of a human hippocampal neuropeptide Y/peptide YY Y2 receptor subtype.. The Journal of biological chemistry, 270(45), 26758-61.