Avtor/Urednik		Floren, Anders; Sollenberg, Ulla; Lundstrom, Linda; Zorko, Matjaž; Stojan, Jure; Budihna, Metka; Wheatley, Mark; Martin, Negin P; Kilk, Kalle; Mazarati, Andrey
Naslov		Multiple interaction sites of galnon trigger its biological effects
Tip		članek
Vir		Neuropeptides
Vol. in št.		Letnik 39
Leto izdaje		2005
Obseg		str. 547-58
Jezik		eng
Abstrakt		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, Ga1R1, Ga1R2 and Ga1R3. Consequently, it was possible that galnon generates its manifold effects by interacting with other signaling pathway components, in addition to via Ga1R1-3. 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 Ga1R1-3. We conclude that galnon has multiple sites of interaction within the GPCR signaling cascade which mediate its physiological effects.
Deskriptorji		GTP-BINDING PROTEINS GALANIN TRANSFECTION CORONARY VESSELS PERTUSSIS TOXINS RATS, WISTAR SWINE SEIZURES CELLS, CULTURED FLUOROMETRY BINDING SITES RADIOLIGAND ASSAY SPECTRUM ANALYSIS, MASS