Effect of palmitoylated prolactin-releasing peptide on food intake and neural activation after different routes of peripheral administration in rats
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26643957
DOI
10.1016/j.peptides.2015.11.005
PII: S0196-9781(15)30005-X
Knihovny.cz E-zdroje
- Klíčová slova
- CD spectroscopy, Food intake, Lipidization, Pharmacokinetics, Prolactin-releasing peptide, c-Fos,
- MeSH
- CHO buňky MeSH
- Cricetulus MeSH
- energetický příjem účinky léků MeSH
- hormon uvolňující prolaktin aplikace a dávkování analogy a deriváty metabolismus farmakokinetika MeSH
- křečci praví MeSH
- krysa rodu Rattus MeSH
- látky proti obezitě aplikace a dávkování metabolismus farmakokinetika MeSH
- lidé MeSH
- mozek metabolismus MeSH
- neurony účinky léků metabolismus MeSH
- obezita farmakoterapie MeSH
- peptidové fragmenty aplikace a dávkování metabolismus farmakokinetika MeSH
- preklinické hodnocení léčiv MeSH
- protoonkogenní proteiny c-fos metabolismus MeSH
- receptory spřažené s G-proteiny metabolismus MeSH
- vazba proteinů MeSH
- zvířata MeSH
- Check Tag
- křečci praví MeSH
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- hormon uvolňující prolaktin MeSH
- látky proti obezitě MeSH
- palmitoyl-PrRP31 peptide, human MeSH Prohlížeč
- peptidové fragmenty MeSH
- PRLHR protein, human MeSH Prohlížeč
- protoonkogenní proteiny c-fos MeSH
- receptory spřažené s G-proteiny MeSH
Obesity is an escalating epidemic, but an effective non-invasive therapy is still scarce. For obesity treatment, anorexigenic neuropeptides are promising tools, but their delivery from the periphery to the brain is complicated by their peptide character. In order to overcome this unfavorable fact, we have applied the lipidization of neuropeptide prolactin-releasing peptide (PrRP), whose strong anorexigenic effect was demonstrated. A palmitoylated analog of human PrRP (h palm-PrRP31) was injected in free-fed Wistar rats by three routes: subcutaneous (s.c.), intraperitoneal (i.p) (both 5 mg/kg) and intravenous (i.v.) (from 0.01 to 0.5 mg/kg). We found a circulating compound in the blood after all three applications with the highest concentration after i.v. administration. This corresponds to the effect on food intake, which was also strongest after i.v. injection. Moreover, this is in agreement with the fact that the expression of c-Fos in specific brain regions involved in food intake regulation was also highest after intravenous application. Pharmacokinetic data are further supported by results obtained from dynamic light scattering and CD spectroscopy. Human palm-PrRP31 analog showed a strong tendency to micellize, and formation of aggregates suggested lower availability after i.p. or s.c. application. We have demonstrated that palm-PrRP influenced food intake even in free fed rats. Not surprisingly, the maximal effect was achieved after the intravenous application even though two orders of magnitude lower dose was used compared to both two other applications. We believe that palm-PrRP could have a potential as an antiobesity drug when its s.c. application would be improved.
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