Effect of palmitoylated prolactin-releasing peptide on food intake and neural activation after different routes of peripheral administration in rats

Mikulášková, Barbora; Zemenová, Jana; Pirník, Zdeno; Pražienková, Veronika; Bednářová, Lucie; Železná, Blanka; Maletı́nská, Lenka; Kuneš, Jaroslav

doi:10.1016/j.peptides.2015.11.005

Cited by 22 publications

(18 citation statements)

References 46 publications

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“…In free-fed Wistar rats, palm-PrRP31 strongly reduced food intake when injected peripherally. Peripheral injection of palm-PrRP31 induced the increase of c-Fos protein in the PVN, NTS, and ARC, which are specific brain regions that are involved in food intake regulation [86].…”

Section: Prrp In the Regulation Of Food Intake And Energy Expenditurementioning

confidence: 99%

Prolactin-Releasing Peptide: Physiological and Pharmacological Properties

Pražienková

Popelová

Kuneš

et al. 2019

IJMS

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Prolactin-releasing peptide (PrRP) belongs to the large RF-amide neuropeptide family with a conserved Arg-Phe-amide motif at the C-terminus. PrRP plays a main role in the regulation of food intake and energy expenditure. This review focuses not only on the physiological functions of PrRP, but also on its pharmacological properties and the actions of its G-protein coupled receptor, GPR10. Special attention is paid to structure-activity relationship studies on PrRP and its analogs as well as to their effect on different physiological functions, mainly their anorexigenic and neuroprotective features and the regulation of the cardiovascular system, pain, and stress. Additionally, the therapeutic potential of this peptide and its analogs is explored.

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Section: Prrp In the Regulation Of Food Intake And Energy Expenditurementioning

confidence: 99%

Prolactin-Releasing Peptide: Physiological and Pharmacological Properties

Pražienková

Popelová

Kuneš

et al. 2019

IJMS

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“…Palmitoylation is one method for the lipidation of a molecule. Recently, the beneficial effects of the palmitoylation of a parental peptide molecule have been shown [ 33 ]. Though the effects of the lipidation of a parent molecule on blood-brain barrier (BBB) penetration have not been documented, hydrophobic small molecules with higher log-P values show better penetration across the BBB, compared to their parental hydrophilic congeners [ 34 ].…”

Section: Introductionmentioning

confidence: 99%

Effects of Three Lipidated Oxytocin Analogs on Behavioral Deficits in CD38 Knockout Mice

et al. 2017

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Oxytocin (OT) is a nonapeptide that plays an important role in social behavior. Nasal administration of OT has been shown to improve trust in healthy humans and social interaction in autistic subjects. As is consistent with the nature of a peptide, OT has some unfavorable characteristics: it has a short half-life in plasma and shows poor permeability across the blood-brain barrier. Analogs with long-lasting effects may overcome these drawbacks. To this end, we have synthesized three analogs: lipo-oxytocin-1 (LOT-1), in which two palmitoyl groups are conjugated to the cysteine and tyrosine residues, lipo-oxytocin-2 (LOT-2) and lipo-oxytocin-3 (LOT-3), which include one palmitoyl group conjugated at the cysteine or tyrosine residue, respectively. The following behavioral deficits were observed in CD38 knockout (CD38−/−) mice: a lack of paternal nurturing in CD38−/− sires, decreased ability for social recognition, and decreased sucrose consumption. OT demonstrated the ability to recover these disturbances to the level of wild-type mice for 30 min after injection. LOT-2 and LOT-3 partially recovered the behaviors for a short period. Conversely, LOT-1 restored the behavioral parameters, not for 30 min, but for 24 h. These data suggest that the lipidation of OT has some therapeutic benefits, and LOT-1 would be most useful because of its long-last activity.

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“…Both myr-PrRP20 and palm-PrRP31 significantly enhanced c-Fos immunoreactivity in hypothalamic and brainstem nuclei involved in food intake regulation (PVN, NTS) and containing both GPR10 and NPFF2 receptors (Roland et al 1999), whereas natural and octanoylated PrRP31 did not . In addition, double c-Fos-GPR10 immunostaining in brainstem C1/A1 cells group indicated that the neurons containing GPR10 receptors are activated after palmPrRP31 administration with intensity depending on the route of its peripheral administration (intravenous administration, compared with subcutaneous or intraperitoneal injection) caused the highest level of c-Fos activation in rats (Mikulášková et al 2015).…”

Section: Lipidized Prrp Analogs As Potential Antiobesity Drugsmentioning

confidence: 93%

“…This may relate to the speed at which palm-PrRP31 is released from the subcutis, optionally with other unknown factors. Nevertheless, we have suggested that palmitoylation of the peptide probably enabled its central effect and stabilization in plasma (Mikulášková et al 2015). However, the new specific conditions should be found for SC administration of palm-PrRP31 to decrease its dose for SC administration based on effective IV doses.…”

Section: Lipidized Prrp Analogs As Potential Antiobesity Drugsmentioning

confidence: 97%

“…Moreover, short-lasted repeated (three injections) administration of palm-PrRP31 to free-fed rats decreased food intake using different routes of palm-PrRP31 delivery: SC, intraperitoneal (IP) or intravenous (IV) (Mikulášková et al 2015). In all cases, food intake 1DMe, stable analog of neuropeptide FF (NPFF); Myr, myristoyl, palm-palmitoyl; SC, subcutaneous.…”

Section: Lipidized Prrp Analogs As Potential Antiobesity Drugsmentioning

confidence: 99%

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Prolactin-releasing peptide: a new tool for obesity treatment

Kuneš

Pražienková

Popelová

et al. 2016

Journal of Endocrinology

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Obesity is an escalating epidemic, but an effective noninvasive therapy is still scarce. For obesity treatment, anorexigenic neuropeptides are promising tools, but their delivery from the periphery to the brain is complicated because peptides have a low stability and limited ability to cross the blood-brain barrier. In this review, we summarize results of several studies with our newly designed lipidized analogs of prolactin-releasing peptide (PrRP). PrRP is involved in feeding and energy balance regulation as demonstrated by obesity phenotypes of both PrRP-and PrRP-receptor-knockout mice. Lipidized PrRP analogs showed binding affinity and signaling in PrRP receptor-expressing cells similar to natural PrRP. Moreover, these analogs showed high binding affinity also to anorexigenic neuropeptide FF (NPFF)-2 receptor. Acute peripheral administration of myristoylated and palmitoylated PrRP analogs to mice and rats induced strong and long-lasting anorexigenic effects and neuronal activation in the brain areas involved in food intake regulation. Two-week-long subcutaneous administration of palmitoylated PrRP31 and myristoylated PrRP20 lowered food intake, body weight, improved metabolic parameters and attenuated lipogenesis in mice with diet-induced obesity. A strong anorexigenic, body weight-reducing and glucose tolerance-improving effect of palmitoylated-PrRP31 was shown also in diet-induced obese rats after its repeated 2-week-long peripheral administration. Thus, the strong anorexigenic and body weight-reducing effects of palmitoylated PrRP31 and myristoylated PrRP20 make these analogs attractive candidates for antiobesity treatment. Moreover, PrRP receptor might be a new target for obesity therapy.

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Effect of palmitoylated prolactin-releasing peptide on food intake and neural activation after different routes of peripheral administration in rats

Cited by 22 publications

References 46 publications

Prolactin-Releasing Peptide: Physiological and Pharmacological Properties

Prolactin-Releasing Peptide: Physiological and Pharmacological Properties

Effects of Three Lipidated Oxytocin Analogs on Behavioral Deficits in CD38 Knockout Mice

Prolactin-releasing peptide: a new tool for obesity treatment

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