[Leu31, Pro34]neuropeptide Y: a specific Y1 receptor agonist
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[Leu31, Pro34]neuropeptide Y : a specific Y1 receptor agonist. / Fuhlendorff, J; Gether, U; Aakerlund, L; Langeland-Johansen, N; Thøgersen, H; Melberg, S G; Olsen, U B; Thastrup, Ole; Schwartz, T W.
In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 87, No. 1, 1990, p. 182-6.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - [Leu31, Pro34]neuropeptide Y
T2 - a specific Y1 receptor agonist
AU - Fuhlendorff, J
AU - Gether, U
AU - Aakerlund, L
AU - Langeland-Johansen, N
AU - Thøgersen, H
AU - Melberg, S G
AU - Olsen, U B
AU - Thastrup, Ole
AU - Schwartz, T W
PY - 1990
Y1 - 1990
N2 - 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.
AB - 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.
KW - Amino Acid Sequence
KW - Animals
KW - Binding, Competitive
KW - Blood Pressure
KW - Calcium
KW - Cell Line
KW - Female
KW - Heart Rate
KW - Humans
KW - Indicators and Reagents
KW - Kinetics
KW - Molecular Sequence Data
KW - Neuropeptide Y
KW - Rats
KW - Rats, Inbred Strains
KW - Receptors, Neuropeptide Y
KW - Receptors, Neurotransmitter
M3 - Journal article
C2 - 2153286
VL - 87
SP - 182
EP - 186
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 1
ER -
ID: 43349917