Cloning the Y4 Receptor — A New Target for Appetite-Controlling Peptide Drugs | Research

The takeaway

The human Y4 receptor was cloned and shown to bind pancreatic polypeptide, NPY, and PYY — expanding the receptor family for these powerful appetite regulators.

New drug target cloned
Y4 is only the second NPY-family receptor cloned, binding three powerful appetite-regulating peptides

What the researchers found

The human Y4 receptor was cloned and shown to bind pancreatic polypeptide, NPY, and PYY, expanding the known receptor family for these appetite-regulating peptides.

Why it matters

NPY and related peptides are among the most powerful appetite stimulators known. Identifying their receptors is essential for developing drugs that could block excessive appetite or treat eating disorders.

How the study worked

Researchers used homology screening of a human placental genomic library to clone the Y4 receptor, then expressed it in cells and characterized its pharmacology using binding and functional assays.

What this study cannot tell us

In vitro characterization of a cloned receptor. Cell-based expression may not fully represent how the receptor behaves in its natural tissue context.

How to read the evidence

Strong — molecular cloning and functional expression with comprehensive binding characterization. Landmark receptor identification.

When this study was published

Published in 1995 (31 years ago). The NPY receptor family has since been fully characterized, with several drug development programs.

The bigger picture

NPY is one of the strongest appetite stimulators known. Cloning its receptors is essential for developing anti-obesity drugs that could block or modulate the powerful hunger signals these peptides transmit.

Questions still open

Can Y4-selective drugs control appetite without other NPY system side effects?
Is Y4 receptor expression altered in obesity?

Common questions

What are NPY and PYY?

NPY (neuropeptide Y) is one of the most powerful appetite-stimulating molecules in the brain. PYY (peptide YY) is released from the gut after eating and signals fullness. Both work through Y-type receptors to control eating behavior.

Could drugs targeting Y4 help with obesity?

Potentially. By understanding which receptor subtypes control which aspects of appetite, scientists can design drugs that reduce hunger or increase fullness without affecting anxiety, blood pressure, or other functions these peptides also regulate.

Read the original research

Cloning and functional expression of a human Y4 subtype receptor for pancreatic polypeptide, neuropeptide Y, and peptide YY.

The Journal of biological chemistry, 270(45), 26762-5

View on PubMed ↗

Citation

Bard, J A; Walker, M W; Branchek, T A; Weinshank, R L. (1995). Cloning and functional expression of a human Y4 subtype receptor for pancreatic polypeptide, neuropeptide Y, and peptide YY.. The Journal of biological chemistry, 270(45), 26762-5.