Peptide YY (PYY) is a 36 amino-acid peptide produced predominantly by endocrine L cells of the ileum, colon and rectum. Food intake releases PYY into the systemic circulation where it regulates gastric emptying, intestinal fluid and electrolyte secretion, gallbladder contraction, and exocrine pancreatic secretion. The two major molecular forms of PYY found in the gut and circulation are PYY(1-36) and PYY(3-36). PYY is a member of the PP-fold family of peptides which exert receptor-mediated biological effects via a class of related Y receptor subtypes, which includes minimally subtypes Y1, Y2, Y4, Y5, Y6, and a PYY preferring receptor (PYY-PrR). PYY(1-36) does not select between Y1, Y2, Y5, and PYY-PrR receptor subtypes. PYY(3-36) binds selectively to Y2 and Y5 receptors, while the proenzyme Pro34-PYY binds selectively to Y1, Y5, and PYY-PrR receptors.

INNOVATION:  UCLA researchers have found that ligands (PYY(1-36) and Pro34-PYY) that act at peripheral Y1 and/or PYY-PrR receptors increase gastric motility and promote opening of the pyloric sphincter. Additionally, UCLA researchers have shown that the Y2/Y5 ligand PYY(3-36) evokes an inhibitory response on gastric motility. Thus, compounds with affinity for the Y1 and/or PYY-PrR receptors and lacking affinity for the Y2 receptor (which exerts inhibitory effects on gastric emptying) may serve as effective prokinetic agents when administered systemically.

POTENTIAL APPLICATIONS 

• Increased prokinetic activity may be obtained by the simultaneous use of a Y2 receptor antagonist with a Y1 and/or PYY-PrR receptor agonist.
• This invention may prove an effective approach for the treatment of gastric ileus (including post-operative gastric ileus) and other functional disorders of the stomach, e.g. functional dyspepsia, that result in or from reduced gastric emptying

Reference: UCLA Case No. 2005-741