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Article

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

1
Biochemistry and Molecular Biology, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, 16610 Prague, Czech Republic
2
First Faculty of Medicine, Charles University, 12108 Prague, Czech Republic
3
Experimental Hypertension, Institute of Physiology of the Czech Academy of Sciences, 14200 Prague, Czech Republic
*
Author to whom correspondence should be addressed.
Academic Editor: Clara Balsano
Int. J. Mol. Sci. 2021, 22(16), 8904; https://doi.org/10.3390/ijms22168904
Received: 1 July 2021 / Revised: 10 August 2021 / Accepted: 12 August 2021 / Published: 18 August 2021
(This article belongs to the Special Issue Neuropeptides in Food Intake Regulation)
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, palm11-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, palm11-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). Palm11-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 (Y1, Y2 and Y5) receptors. Palm11-PrRP31 exhibited fewer off-target activities; therefore, it has a higher potential to be used as an anti-obesity drug with anorectic effects. View Full-Text
Keywords: prolactin-releasing peptide; GPR10; neuropeptide FF; NPFF-R2; NPFF-R1; binding properties; signaling pathways prolactin-releasing peptide; GPR10; neuropeptide FF; NPFF-R2; NPFF-R1; binding properties; signaling pathways
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MDPI and ACS Style

Karnošová, A.; Strnadová, V.; Holá, L.; Železná, B.; Kuneš, J.; Maletínská, L. Palmitoylation of Prolactin-Releasing Peptide Increased Affinity for and Activation of the GPR10, NPFF-R2 and NPFF-R1 Receptors: In Vitro Study. Int. J. Mol. Sci. 2021, 22, 8904. https://doi.org/10.3390/ijms22168904

AMA Style

Karnošová A, Strnadová V, Holá L, Železná B, Kuneš J, 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. 2021; 22(16):8904. https://doi.org/10.3390/ijms22168904

Chicago/Turabian Style

Karnošová, Alena, Veronika Strnadová, Lucie Holá, Blanka Železná, Jaroslav Kuneš, and Lenka Maletínská. 2021. "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 22, no. 16: 8904. https://doi.org/10.3390/ijms22168904

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