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Palmitoylation of Prolactin-Releasing Peptide Increased Affinity for and Activation of the GPR10, NPFF-R2 and NPFF-R1 Receptors: In Vitro Study
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SYSNO ASEP 0545497 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Palmitoylation of Prolactin-Releasing Peptide Increased Affinity for and Activation of the GPR10, NPFF-R2 and NPFF-R1 Receptors: In Vitro Study Author(s) Karnošová, A. (CZ)
Strnadová, V. (CZ)
Holá, L. (CZ)
Železná, B. (CZ)
Kuneš, Jaroslav (FGU-C) RID, ORCID
Maletínská, L. (CZ)Article number 8904 Source Title International Journal of Molecular Sciences. - : MDPI
Roč. 22, č. 16 (2021)Number of pages 17 s. Language eng - English Country CH - Switzerland Keywords prolactin-releasing peptide ; GPR10 ; neuropeptide FF ; NPFF-R2 ; NPFF-R1 ; binding properties ; signaling pathways Subject RIV ED - Physiology OECD category Physiology (including cytology) R&D Projects GA21-03691S GA ČR - Czech Science Foundation (CSF) Method of publishing Open access Institutional support FGU-C - RVO:67985823 UT WOS 000689129400001 EID SCOPUS 85112686217 DOI 10.3390/ijms22168904 Annotation 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. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2022 Electronic address https://www.mdpi.com/1422-0067/22/16/8904
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