Novel generation of hormone receptor specificity by amino terminal processing of peptide YY.
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.
Grandt
D
D
University of Essen, Division of Gastroenterology, Germany.
Teyssen
S
S
Schimiczek
M
M
Reeve
J R
JR
Feth
F
F
Rascher
W
W
Hirche
H
H
Singer
M V
MV
Layer
P
P
Goebell
H
H
D000818:Animals; D001667:Binding, Competitive; D002460:Cell Line; D002108:Ceruletide / Q000378:metabolism; D004285:Dogs; D005260:Female; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D006801:Humans; D008297:Male; D009447:Neuroblastoma; D009478:Neuropeptide Y / Q000378:metabolism*; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D019894:Peptide YY; D010455:Peptides / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012633:Secretin / Q000378:metabolism*; D013379:Substrate Specificity
D005768:Gastrointestinal Hormones; D009478:Neuropeptide Y; D010455:Peptides; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter; D019894:Peptide YY; D012633:Secretin; D002108:Ceruletide