Biological properties of prolactin-releasing peptide analogs with a modified aromatic ring of a C-terminal phenylalanine amide
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21872625
DOI
10.1016/j.peptides.2011.08.011
PII: S0196-9781(11)00330-5
Knihovny.cz E-resources
- MeSH
- Appetite Depressants administration & dosage pharmacology MeSH
- Phenylalanine analogs & derivatives metabolism MeSH
- Phosphorylation MeSH
- Prolactin-Releasing Hormone administration & dosage analogs & derivatives pharmacology MeSH
- Rats MeSH
- Mitogen-Activated Protein Kinases metabolism MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Fasting physiology MeSH
- Eating drug effects physiology MeSH
- Prolactin metabolism MeSH
- CREB-Binding Protein metabolism MeSH
- Receptors, Neuropeptide metabolism MeSH
- Receptors, G-Protein-Coupled metabolism MeSH
- Signal Transduction MeSH
- Protein Binding MeSH
- Structure-Activity Relationship MeSH
- Blotting, Western MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Appetite Depressants MeSH
- Crebbp protein, rat MeSH Browser
- Phenylalanine MeSH
- Prolactin-Releasing Hormone MeSH
- Mitogen-Activated Protein Kinases MeSH
- phenylalanine amide MeSH Browser
- Prlhr protein, mouse MeSH Browser
- Prolactin MeSH
- CREB-Binding Protein MeSH
- receptor, prolactin-releasing peptide MeSH Browser
- Receptors, Neuropeptide MeSH
- Receptors, G-Protein-Coupled MeSH
Prolactin-releasing peptide (PrRP)-induced secretion of prolactin is not currently considered a primary function of PrRP, but the development of late-onset obesity in both PrRP and PrRP receptor knock-out mice indicates the unique anorexigenic properties of PrRP. In our recent study, we showed comparable potencies of peptides PrRP31 and PrRP20 in binding, intracellular signaling and prolactin release in pituitary RC-4B/C cells, and anorexigenic effect after central administration in fasted mice. In the present study, eight analogs of PrRP20 with C-terminal Phe amide modified with a bulky side chain or a halogenated aromatic ring revealed high binding potency, activation of mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK1/2) and cAMP response element-binding protein (CREB) and prolactin release in RC-4B/C cells. In particular, [PheNO(2)(31)]PrRP20, [1-Nal(31)]PrRP20, [2-Nal(31)]PrRP20 and [Tyr(31)]PrRP20 showed not only in vitro effects comparable or higher than those of PrRP20, but also a very significant and long-lasting anorexigenic effect after central administration in fasted mice. The design of potent and long-lasting PrRP analogs with selective anorexigenic properties promises to contribute to the study of food intake disorders.
References provided by Crossref.org
Prolactin-Releasing Peptide: Physiological and Pharmacological Properties
