title: Biological properties of prolactin-releasing peptide analogs with a modified aromatic ring of a C-terminal phenylalanine amide.
abstract: 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.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Flemingovo nám. 2, Prague 6, Czech Republic. maletin@uochb.cas.cz
authors.forename: Lenka
authors.initials: L
authors.lastname: Maletínská
authors.forename: Andrea
authors.initials: A
authors.lastname: Spolcová
authors.forename: Jana
authors.initials: J
authors.lastname: Maixnerová
authors.forename: Miroslava
authors.initials: M
authors.lastname: Blechová
authors.forename: Blanka
authors.initials: B
authors.lastname: Zelezná
mesh_terms: D000818:Animals; D001067:Appetite Depressants / Q000008:administration & dosage / Q000494:pharmacology*; D015153:Blotting, Western; D050882:CREB-Binding Protein / Q000378:metabolism; D045744:Cell Line, Tumor; D004435:Eating / Q000187:drug effects* / Q000502:physiology; D005215:Fasting / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000378:metabolism; D010766:Phosphorylation; D011388:Prolactin / Q000378:metabolism; D056690:Prolactin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D018013:Receptors, Neuropeptide / Q000378:metabolism; D015398:Signal Transduction; D013329:Structure-Activity Relationship
chemical_list: D001067:Appetite Depressants; C487625:Prlhr protein, mouse; D056690:Prolactin-Releasing Hormone; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C400801:receptor, prolactin-releasing peptide; D010649:Phenylalanine; C020457:phenylalanine amide; D011388:Prolactin; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D020928:Mitogen-Activated Protein Kinases