Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Novel galanin receptor subtype specific ligands in feeding regulation
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry.
Show others and affiliations
2011 (English)In: Neurochemistry International, ISSN 0197-0186, E-ISSN 1872-9754, Vol. 58, no 6, 714-720 p.Article in journal (Refereed) Published
Abstract [en]

Galanin a 29/30-residue neuropeptide has been implicated in several functions in the central nervous system, including the regulation of food consumption. Galanin and its analogues administered intraventricularly or into the hypothalamic region of brain have been shown to reliably and robustly stimulate the consumption of food in sated rodents. Three galanin receptor subtypes have been isolated, all present in the hypothalamus, but little is known about their specific role in mediating this acute feeding response. Presently, we introduce several novel GalR2 selective agonists and then compare the most selective of these novel GalR2 subtype selective agonists to known GalR1 selective agonist M617 for their ability to stimulate acute consumption of several foods shown to be stimulated by central administration of galanin. GalR1 selective agonist M617 markedly stimulated acute consumption of high-fat milk, but neither GalR2 selective agonist affected either high-fat milk or cookie mash intake. The present results are consistent with the involvement of GalR1 in mediating the acute feeding consumption by galanin and suggest an approach applicable to exploring galanin receptor specificity in normal and abnormal behavior and physiology.

Place, publisher, year, edition, pages
2011. Vol. 58, no 6, 714-720 p.
Keyword [en]
Galanin, Galanin receptor type 2, Feeding, Agonist, GPCR, Neuropeptide
National Category
Neurosciences Biochemistry and Molecular Biology
Research subject
Neurochemistry with Molecular Neurobiology
Identifiers
URN: urn:nbn:se:su:diva-68532DOI: 10.1016/j.neuint.2011.02.012ISI: 000290139900014OAI: oai:DiVA.org:su-68532DiVA: diva2:472832
Note
6Available from: 2012-01-04 Created: 2012-01-04 Last updated: 2017-12-08Bibliographically approved
In thesis
1. Delineating Ligand-Receptor Interactions and the Design of Subtype Selective Galanin Receptor Ligands
Open this publication in new window or tab >>Delineating Ligand-Receptor Interactions and the Design of Subtype Selective Galanin Receptor Ligands
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

We now celebrate that it is 30 years since galanin was first isolated. During these three decades galanin has been identified in numerous tissues and physiological processes, and in an abundant number of species. In the nervous system galanin primarily displays a modulatory role. The galaninergic system consists of a number of bioactive peptides with a highlyplastic expression pattern and three different receptors, GalR1-GalR3. The lack of receptor subtype selective ligands and antibodies have severely hampered the characterization of this system. Therefore, most of the knowledgehas been drawn from experiments with transgenic animals, which has givensome major conclusions, despite the risk of inducing compensatory effects inthese animal studies. Therefore, the production of subtype selective ligandsis of great importance to delineate the galanin system and slowly experimental data from receptor subtype selective ligand trials is emerging. This thesis aims at studying galanin receptor-ligand interactions and to increase and improve the utilized tools in the galanin research field, especially the development of novel galanin receptor subtype selective ligands. Paper I demonstrates the potential to N-terminally extend galanin analogues and the successful development of a GalR2 selective ligand. In addition, a cell line stably expressing GalR3 was developed to improve and simplify future evaluations of receptor subtype selective galanin ligands. Paper II extends the number of GalR2 selective ligands and shows that i.c.v. administration of galanin receptor ligands stimulates food intake through GalR1. Paper III demonstrates the successful development of a mixed GalR1/GalR2 agonist without any detectable interaction with GalR3. Subsequently, this peptide was used to delineate which receptor subtype mediatesthe neuroprotective effects of galanin in the CA3 region of hippocampus. Furthermore, a robust protocol for detection of receptor activation was developed to ease the detection of the relative potency of novel ligands at the three galanin receptor subtypes. Paper IV describes the finding of several essential amino acids for ligand interaction in GalR3 through the performance of an L-alanine mutagenesis study. A constructed in silico homology model of GalR3 confirmed and extended these findings. In conclusion, this thesis provides a novel design strategy for galanin receptor ligands and increases the understanding of ligand interactions with the GalR3. Furthermore, published ligands together with new galanin analogues have proven to be highly receptor specific, thus implicating that a future delineation of the galaninergic system as a therapeutic target is possible.

Place, publisher, year, edition, pages
Stockholm: Department of Neurochemistry, Stockholm University, 2012. 96 p.
National Category
Natural Sciences
Research subject
Neurochemistry with Molecular Neurobiology
Identifiers
urn:nbn:se:su:diva-75503 (URN)978-91-7447-503-6 (ISBN)
Public defence
2012-06-01, Magnélisalen, Kemiska övningslaboratoriet, Svante Arrheniusväg 16 B, Stockholm, 13:00 (English)
Opponent
Supervisors
Note
At the time of the doctoral defense, the following paper was unpublished and had a status as follows: Paper 3: Manuscript.Available from: 2012-05-10 Created: 2012-04-20 Last updated: 2015-04-21Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Runesson, JohanLangel, Ülo
By organisation
Department of Neurochemistry
In the same journal
Neurochemistry International
NeurosciencesBiochemistry and Molecular Biology

Search outside of DiVA

GoogleGoogle Scholar

doi
urn-nbn

Altmetric score

doi
urn-nbn
Total: 40 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf