Prolactin-releasing peptide (PrRP) has been proposed to mediate the central satiating effects of cholecystokinin (CCK) through the vagal CCK1 receptor. PrRP acts as an endogenous ligand of G protein-coupled receptor 10 (GPR10), which is expressed at the highest levels in brain areas related to food intake regulation, e.g., the paraventricular hypothalamic nucleus (PVN) and nucleus of the solitary tract (NTS). The NTS and PVN are also significantly activated after peripheral CCK administration. The aim of this study was to determine whether the endogenous PrRP neuronal system in the brain is involved in the central anorexigenic effect of the peripherally administered CCK agonist JMV236 or the CCK1 antagonist devazepide and whether the CCK system is involved in the central anorexigenic effect of the peripherally applied lipidized PrRP analog palm-PrRP31 in fasted lean mice. The effect of devazepide and JMV236 on the anorexigenic effects of palm-PrRP31 as well as devazepide combined with JMV236 and palm-PrRP31 on food intake and Fos cell activation in the PVN and caudal NTS was examined. Our results suggest that the anorexigenic effect of JMV236 is accompanied by activation of PrRP neurons of the NTS in a CCK1 receptor-dependent manner. Moreover, while the anorexigenic effect of palm-PrRP31 was not affected by JMV236, it was partially attenuated by devazepide in fasted mice. The present findings indicate that the exogenously influenced CCK system may be involved in the central anorexigenic effect of peripherally applied palm-PrRP31, which possibly indicates some interaction between the CCK and PrRP neuronal systems.
- MeSH
- anorektika aplikace a dávkování MeSH
- antagonisté hormonů aplikace a dávkování MeSH
- chemokiny CC účinky léků metabolismus MeSH
- cholecystokinin metabolismus MeSH
- devazepid aplikace a dávkování MeSH
- hormon uvolňující prolaktin aplikace a dávkování analogy a deriváty MeSH
- injekce intraperitoneální MeSH
- injekce subkutánní MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nucleus paraventricularis hypothalami účinky léků metabolismus MeSH
- nucleus solitarius účinky léků metabolismus MeSH
- omezení příjmu potravy MeSH
- peptidové fragmenty aplikace a dávkování MeSH
- přijímání potravy účinky léků MeSH
- protoonkogenní proteiny c-fos metabolismus MeSH
- signální transdukce MeSH
- sinkalid aplikace a dávkování analogy a deriváty MeSH
- stravovací zvyklosti účinky léků MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- anorektika MeSH
- antagonisté hormonů MeSH
- Ccl28 protein, mouse MeSH Prohlížeč
- chemokiny CC MeSH
- cholecystokinin MeSH
- devazepid MeSH
- Fos protein, mouse MeSH Prohlížeč
- hormon uvolňující prolaktin MeSH
- JMV 236 MeSH Prohlížeč
- palm11-PrRP31 MeSH Prohlížeč
- peptidové fragmenty MeSH
- protoonkogenní proteiny c-fos MeSH
- sinkalid MeSH
Prolactin-releasing peptide (PrRP)-induced secretion of prolactin is not currently considered a primary function of PrRP, but the development of late-onset obesity in both PrRP and PrRP receptor knock-out mice indicates the unique anorexigenic properties of PrRP. In our recent study, we showed comparable potencies of peptides PrRP31 and PrRP20 in binding, intracellular signaling and prolactin release in pituitary RC-4B/C cells, and anorexigenic effect after central administration in fasted mice. In the present study, eight analogs of PrRP20 with C-terminal Phe amide modified with a bulky side chain or a halogenated aromatic ring revealed high binding potency, activation of mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK1/2) and cAMP response element-binding protein (CREB) and prolactin release in RC-4B/C cells. In particular, [PheNO(2)(31)]PrRP20, [1-Nal(31)]PrRP20, [2-Nal(31)]PrRP20 and [Tyr(31)]PrRP20 showed not only in vitro effects comparable or higher than those of PrRP20, but also a very significant and long-lasting anorexigenic effect after central administration in fasted mice. The design of potent and long-lasting PrRP analogs with selective anorexigenic properties promises to contribute to the study of food intake disorders.
- MeSH
- anorektika aplikace a dávkování farmakologie MeSH
- fenylalanin analogy a deriváty metabolismus MeSH
- fosforylace MeSH
- hormon uvolňující prolaktin aplikace a dávkování analogy a deriváty farmakologie MeSH
- krysa rodu Rattus MeSH
- mitogenem aktivované proteinkinasy metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- nádorové buněčné linie MeSH
- omezení příjmu potravy fyziologie MeSH
- přijímání potravy účinky léků fyziologie MeSH
- prolaktin metabolismus MeSH
- protein vázající CREB metabolismus MeSH
- receptory neuropeptidů metabolismus MeSH
- receptory spřažené s G-proteiny metabolismus MeSH
- signální transdukce MeSH
- vazba proteinů MeSH
- vztahy mezi strukturou a aktivitou MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- anorektika MeSH
- Crebbp protein, rat MeSH Prohlížeč
- fenylalanin MeSH
- hormon uvolňující prolaktin MeSH
- mitogenem aktivované proteinkinasy MeSH
- phenylalanine amide MeSH Prohlížeč
- Prlhr protein, mouse MeSH Prohlížeč
- prolaktin MeSH
- protein vázající CREB MeSH
- receptor, prolactin-releasing peptide MeSH Prohlížeč
- receptory neuropeptidů MeSH
- receptory spřažené s G-proteiny MeSH
