Multiple interaction sites of galnon trigger its biological effects

Anders Florén, Ulla Sollenberg, Linda Lundström, Matjaž Zorko, Jure Stojan, Metka Budihna, Mark Wheatley, Negin P. Martin, Kalle Kilk, Andrey Mazarati, Tamas Bartfai, Maria Lindgren, Ülo Langel

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Galnon was first reported as a low molecular weight non-peptide agonist at galanin receptors [Saar et al. (2002) Proc. Natl. Acad. Sci. USA 99, 7136-7141]. Following its systemic administration, this synthetic ligand affected a range of important physiological processes including appetite, seizures and pain. Physiological activity of galnon could not be explained solely by the activation of the three known galanin receptors, GalR1, GalR2 and GalR3. Consequently, it was possible that galnon generates its manifold effects by interacting with other signaling pathway components, in addition to via GalR1-3. In this report, we establish that galnon: (i) can penetrate across the plasma membrane of cells, (ii) can activate intracellular G-proteins directly independent of receptor activation thereby triggering downstream signaling, (iii) demonstrates selectivity for different G-proteins, and (iiii) is a ligand to other G-protein coupled receptors (GPCRs) in addition to via GalR1-3. We conclude that galnon has multiple sites of interaction within the GPCR signaling cascade which mediate its physiological effects.

Original languageEnglish
Pages (from-to)547-558
Number of pages12
JournalNeuropeptides
Volume39
Issue number6
Early online date16 Nov 2005
DOIs
Publication statusPublished - Dec 2005
Externally publishedYes

Keywords

  • G-protein
  • Galanin
  • Galnon
  • Receptor
  • Signaling

ASJC Scopus subject areas

  • Endocrinology
  • Neurology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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