[Leu31, Pro34]neuropeptide Y: a specific Y1 receptor agonist.
Two types of binding sites have previously been described for 36-amino acid neuropeptide Y (NPY), called Y1 and Y2 receptors. Y2 receptors can bind long C-terminal fragments of NPY-e.g., NPY-(13-36)-peptide. In contrast, Y1 receptors have until now only been characterized as NPY receptors that do not bind such fragments. In the present study an NPY analog is presented, [Leu31, Pro34]NPY, which in a series of human neuroblastoma cell lines and on rat PC-12 cells can displace radiolabeled NPY only from cells that express Y1 receptors and not from those expressing Y2 receptors. The radiolabeled analog, [125I-Tyr36] monoiodo-[Leu31, Pro34]NPY, also binds specifically only to cells with Y1 receptors. The binding of this analog to Y1 receptors on human neuroblastoma cells is associated with a transient increase in cytoplasmic free calcium concentrations similar to the response observed with NPY. [Leu31, Pro34]NPY is also active in vivo as it is even more potent than NPY in increasing blood pressure in anesthetized rats. It is concluded that [Leu31, Pro34]NPY is a specific Y1 receptor agonist and that the analog or variants of it can be useful in delineating the physiological importance of Y1 receptors.
Fuhlendorff
J
J
University Department of Clinical Chemistry, Rigshospitalet, Copenhagen, Denmark.
Gether
U
U
Aakerlund
L
L
Langeland-Johansen
N
N
Thøgersen
H
H
Melberg
S G
SG
Olsen
U B
UB
Thastrup
O
O
Schwartz
T W
TW
D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000378:metabolism
D007202:Indicators and Reagents; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D017981:Receptors, Neurotransmitter; C062259:neuropeptide Y, Leu(31)-Pro(34)-; D002118:Calcium