Pharmacological characterization of lipidized analogs of prolactin-releasing peptide with a modified C- terminal aromatic ring.
J Physiol Pharmacol
; 67(1): 121-8, 2016 Feb.
Article
en En
| MEDLINE
| ID: mdl-27010901
Prolactin-releasing peptide (PrRP) is an anorexigenic neuropeptide expressed in the brain where it regulates food intake and energy expenditure. The C-terminal Arg-Phe-NH2 of PrRP is crucial for its biological activity. In our previous study, we showed that PrRP analogs myristoylated or palmitoylated at the N- terminus seem to cross the blood-brain barrier and lower food intake following peripheral administration. In this study, myristoylated and palmitoylated PrRP31 analogs with a modified C-terminal Phe were designed and tested. Lipidized analogs containing Phe(31) replaced by aromatic non-coded amino acids or tyrosine revealed high binding affinity to rat pituitary RC-4B/C cells with endogenous PrRP and neuropeptide FF 2 receptors and to CHO-K1 cells overexpressing either PrRP or neuropeptide FF 2 receptors. The analogs also showed strong agonistic properties at the GPR10 receptor using the beta-lactamase reporter gene assay. Moreover, lipidized PrRP analogs, especially those that were palmitoylated, demonstrated strong and long-lasting anorexigenic effects in fasted mice after subcutaneous administration. The most efficient PrRP31 analogs with PheCl2(31), either palmitoylated or myristoylated at the N-terminus, are promising candidates for the study of food disorders, possibly for anti-obesity treatment. Despite the therapeutic potential in targeting central GPR10, the endogenous ligand PrRP cannot cross the blood-brain barrier. Understanding biological activity and transport of novel structural analogs of PrRP with a potential central anorexigenic effect is of key therapeutic significance.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neuropéptidos
/
Hormona Liberadora de Prolactina
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
J Physiol Pharmacol
Asunto de la revista:
FARMACOLOGIA
/
FISIOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
República Checa
Pais de publicación:
Polonia