Palmitoylation of Prolactin-Releasing Peptide Increased Affinity for and Activation of the GPR10, NPFF-R2 and NPFF-R1 Receptors: In Vitro Study

0545497 - FGÚ 2022 RIV CH eng J - Journal Article
Karnošová, A. - Strnadová, V. - Holá, L. - Železná, B. - Kuneš, Jaroslav - Maletínská, L.
Palmitoylation of Prolactin-Releasing Peptide Increased Affinity for and Activation of the GPR10, NPFF-R2 and NPFF-R1 Receptors: In Vitro Study.
International Journal of Molecular Sciences. Roč. 22, č. 16 (2021), č. článku 8904. E-ISSN 1422-0067
R&D Projects: GA ČR(CZ) GA21-03691S
Institutional support: RVO:67985823
Keywords : prolactin-releasing peptide * GPR10 * neuropeptide FF * NPFF-R2 * NPFF-R1 * binding properties * signaling pathways
OECD category: Physiology (including cytology)
Impact factor: 6.208, year: 2021
Method of publishing: Open access
https://www.mdpi.com/1422-0067/22/16/8904

The anorexigenic neuropeptide prolactin-releasing peptide (PrRP) is involved in the regulation of food intake and energy expenditure. Lipidization of PrRP stabilizes the peptide, facilitates central effect after peripheral administration and increases its affinity for its receptor, GPR10, and for the neuropeptide FF (NPFF) receptor NPFF-R2. The two most potent palmitoylated analogs with anorectic effects in mice, palm(11)-PrRP31 and palm-PrRP31, were studied in vitro to determine their agonist/antagonist properties and mechanism of action on GPR10, NPFF-R2 and other potential off-target receptors related to energy homeostasis. Palmitoylation of both PrRP31 analogs increased the binding properties of PrRP31 to anorexigenic receptors GPR10 and NPFF-R2 and resulted in a high affinity for another NPFF receptor, NPFF-R1. Moreover, in CHO-K1 cells expressing GPR10, NPFF-R2 or NPFF-R1, palm(11)-PrRP and palm-PrRP significantly increased the phosphorylation of extracellular signal-regulated kinase (ERK), protein kinase B (Akt) and cAMP-responsive element-binding protein (CREB). Palm(11)-PrRP31, unlike palm-PrRP31, did not activate either c-Jun N-terminal kinase (JNK), p38, c-Jun, c-Fos or CREB pathways in cells expressing NPFF-1R. Palm-PrRP31 also has higher binding affinities for off-target receptors, namely, the ghrelin, opioid (KOR, MOR, DOR and OPR-L1) and neuropeptide Y (Y-1, Y-2 and Y-5) receptors. Palm(11)-PrRP31 exhibited fewer off-target activities, therefore, it has a higher potential to be used as an anti-obesity drug with anorectic effects.
Permanent Link: http://hdl.handle.net/11104/0322178