Please use this identifier to cite or link to this item: http://hdl.handle.net/2067/1456
Title: Binding and functional properties of the novel somatostatin analogue KE 108 at native mouse somatostatin receptors
Authors: Cervia, Davide
Langenegger, Daniel
Schuepbach, Edi
Cammalleri, Maurizio
Schoeffter, Philippe
Schmid, Herbert A.
Bagnoli, Paola
Hoyer, Daniel
Keywords: Somatostatin agonists;AtT-20 cells;Mouse hippocampus;Receptor binding;cAMP;Ca2+ regulation;Epilepsy
Issue Date: 2005
Publisher: Elsevier
Source: Cervia, D. et al. 2005. Binding and functional properties of the novel somatostatin analogue KE 108 at native mouse somatostatin receptors. "Neuropharmacology" 48(6): 881-893
Abstract: 
Clinically used somatostatin (SRIF) analogs octreotide and lanreotide act primarily by binding to SRIF receptor subtype 2 (sst2). In contrast, the recently described multiligand SOM230 binds with high affinity to sst1-3 and sst5 and KE 108 is characterised as a high affinity ligand for all five SRIF receptors. In tumoural mouse corticotrophs (AtT-20 cells) and in mouse hippocampus, binding and functional features of KE 108 were examined and compared to SRIF-14, octreotide and SOM230.
In AtT-20 cells, KE 108 bound with high affinity at [125I]LTT-SRIF-28-labelled sites similarly to SRIF, octreotide and SOM230. At the functional level, all four ligands increased guanosine-5’--(3-35Sthio)-triphosphate binding and decreased cAMP accumulation or intracellular Ca2+ concentration through Gi/o proteins. In hippocampal slices, KE 108, octreotide and SOM230 also bound with high affinity at [125I]LTT-SRIF-28-labelled sites similarly to SRIF, but KE108, octreotide or SOM230 did not influence spontaneous epileptiform activity which was, in contrast, inhibited by SRIF.
In conclusion, this study demonstrates that KE 108 has high affinity for native mouse SRIF receptors. Functionally, KE 108 mediates SRIF action at sst2/5 in corticotrophs whereas it does not mimic the SRIF-induced inhibition of hippocampal excitation suggesting that the high potency and efficacy of a synthetic ligand to all known SRIF receptors may not reproduce entirely the effects of the natural SRIF.
Description: 
L'articolo è disponibile sul sito dell'editore http://www.sciencedirect.com/
URI: http://hdl.handle.net/2067/1456
ISSN: 0028-3908
DOI: 10.1016/j.neuropharm.2004.12.019
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