title: Effect of palmitoylated prolactin-releasing peptide on food intake and neural activation after different routes of peripheral administration in rats.
abstract: 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.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Czech Republic; Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
authors.forename: Barbora
authors.initials: B
authors.lastname: Mikulášková
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Czech Republic; University of Chemistry and Technology, Department of Analytical Chemistry, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Zemenová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Czech Republic; Laboratory of Functional Neuromorphology, Institute of Experimental Endocrinology, SAS, Bratislava, Slovak Republic; Department of Human and Clinical Pharmacology, University of Veterinary Medicine, Košice, Slovak Republic.
authors.forename: Zdenko
authors.initials: Z
authors.lastname: Pirník
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Pražienková
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Czech Republic.
authors.forename: Lucie
authors.initials: L
authors.lastname: Bednárová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Czech Republic.
authors.forename: Blanka
authors.initials: B
authors.lastname: Železná
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Maletínská
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Czech Republic; Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. Electronic address: kunes@biomed.cas.cz.
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Kuneš
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical; D002149:Energy Intake / Q000187:drug effects*; D006801:Humans; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000378:metabolism / Q000493:pharmacokinetics; D056690:Prolactin-Releasing Hormone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D011485:Protein Binding; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism
chemical_list: D019440:Anti-Obesity Agents; C112345:PRLHR protein, human; D010446:Peptide Fragments; D056690:Prolactin-Releasing Hormone; D016760:Proto-Oncogene Proteins c-fos; D043562:Receptors, G-Protein-Coupled; C000611667:palmitoyl-PrRP31 peptide, human
keywords: CD spectroscopy; Food intake; Lipidization; Pharmacokinetics; Prolactin-releasing peptide; c-Fos