Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9118943 | Neuropeptides | 2005 | 12 Pages |
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.
Keywords
5-HTPTXAVPGPCRV1aRmAChR5-hydroxytryptamineSSSETFAIC50adrenoreceptorOTRV2RV2 vasopressin receptorHKRGalnonV1a vasopressin receptor[Arg8]vasopressinPBSDMSOG-protein coupled receptorsPpsTrifluoroacetic acidChoperforant path stimulationChinese Hamster Ovaryself-sustaining status epilepticusDimethylsulfoxidepertussis toxinSignalingPhosphate buffered salinelactate dehydrogenaseLDHMALDI-TOF MSReverse phaseG-proteinhigh performance liquid chromatographyHPLCGalRGalaninReceptoroxytocin receptorgalanin receptor
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Authors
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, Ãlo Langel,