Novel Generation of Hormone Receptor Specificity by Amino Terminal Processing of Peptide YY

Biochem Biophys Res Commun. 1992 Aug 14;186(3):1299-306. doi: 10.1016/s0006-291x(05)81547-5.

Abstract

The physiological significance of multiple Y receptors has not been determined since until recently only one form of endogenous agonists was known, namely PYY1-36 and NPY1-36. Recently, a new molecular form of PYY was characterized as des(Tyr-Pro)PYY (PYY3-36 or PYY-II). Its ability to interact at various Y receptors was not characterized. Analytical chromatography of fresh canine colon extracts shows two peaks of immunoreactivity eluting in the positions of PYY-II and PYY1-36 (PYY). PYY-II was about 40% of the total PYY immunoreactivity indicating that it is one of the major forms of PYY expressing its biological activity. It is shown that PYY-II will not displace label from the Y1 receptors found on a human neuroblastoma cell line. It is further shown that PYY-II is as potent as PYY for the inhibition of pancreatic secretion, which must occur through Y2 receptors. The enzymatic removal of Tyr-Pro from PYY to form PYY-II must therefore regulate the relative expression of a non-selective agonist (PYY) to a highly selective Y2 agonist (PYY-II). Amino terminal processing of PYY represents a novel type of regulation of peptide hormone specificity. It has important biological implications for PYY and potential relevance for other peptide hormone receptor systems.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding, Competitive
  • Cell Line
  • Ceruletide / metabolism
  • Dogs
  • Female
  • Gastrointestinal Hormones / metabolism*
  • Humans
  • Male
  • Neuroblastoma
  • Neuropeptide Y / metabolism*
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Peptide YY
  • Peptides / genetics
  • Peptides / metabolism*
  • Peptides / pharmacology*
  • Protein Processing, Post-Translational*
  • Receptors, Neuropeptide Y
  • Receptors, Neurotransmitter / metabolism*
  • Secretin / metabolism*
  • Substrate Specificity

Substances

  • Gastrointestinal Hormones
  • Neuropeptide Y
  • Peptides
  • Receptors, Neuropeptide Y
  • Receptors, Neurotransmitter
  • Peptide YY
  • Secretin
  • Ceruletide