Abstract
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.
| Original language | English |
|---|---|
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 87 |
| Issue number | 1 |
| Pages (from-to) | 182-6 |
| Number of pages | 5 |
| ISSN | 0027-8424 |
| Publication status | Published - 1990 |
Keywords
- Amino Acid Sequence
- Animals
- Binding, Competitive
- Blood Pressure
- Calcium
- Cell Line
- Female
- Heart Rate
- Humans
- Indicators and Reagents
- Kinetics
- Molecular Sequence Data
- Neuropeptide Y
- Rats
- Rats, Inbred Strains
- Receptors, Neuropeptide Y
- Receptors, Neurotransmitter