Effect of palmitoylated prolactin-releasing peptide on food intake and neural activation after different routes of peripheral administration in rats
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26643957
DOI
10.1016/j.peptides.2015.11.005
PII: S0196-9781(15)30005-X
Knihovny.cz E-resources
- Keywords
- CD spectroscopy, Food intake, Lipidization, Pharmacokinetics, Prolactin-releasing peptide, c-Fos,
- MeSH
- CHO Cells MeSH
- Cricetulus MeSH
- Energy Intake drug effects MeSH
- Prolactin-Releasing Hormone administration & dosage analogs & derivatives metabolism pharmacokinetics MeSH
- Cricetinae MeSH
- Rats MeSH
- Anti-Obesity Agents administration & dosage metabolism pharmacokinetics MeSH
- Humans MeSH
- Brain metabolism MeSH
- Neurons drug effects metabolism MeSH
- Obesity drug therapy MeSH
- Peptide Fragments administration & dosage metabolism pharmacokinetics MeSH
- Drug Evaluation, Preclinical MeSH
- Proto-Oncogene Proteins c-fos metabolism MeSH
- Receptors, G-Protein-Coupled metabolism MeSH
- Protein Binding MeSH
- Animals MeSH
- Check Tag
- Cricetinae MeSH
- Rats MeSH
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Prolactin-Releasing Hormone MeSH
- Anti-Obesity Agents MeSH
- palmitoyl-PrRP31 peptide, human MeSH Browser
- Peptide Fragments MeSH
- PRLHR protein, human MeSH Browser
- Proto-Oncogene Proteins c-fos MeSH
- Receptors, G-Protein-Coupled 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.
References provided by Crossref.org
Ultra-inert lanthanide chelates as mass tags for multiplexed bioanalysis
An analogue of the Prolactin Releasing Peptide reduces obesity and promotes adult neurogenesis
Prolactin-Releasing Peptide: Physiological and Pharmacological Properties
