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|Title:||Modulation of the neuronal response to ischemia by somatostatin analogues in wild-type and knock-out mouse retinas||Authors:||Cervia, Davide
Timperio, Anna Maria
|Keywords:||Cell death;G protein-coupled receptor kinases;Glutamate release;Regulators of G protein signalling;Somatostatin receptors||Issue Date:||2008||Publisher:||Wiley-Blackwell||Source:||Cervia, D. et al. 2008. Modulation of the neuronal response to ischemia by somatostatin analogues in wild-type and knock-out mouse retinas. "Journal of Neurochemistry" 106(5): 2224-2235||Abstract:||
Somatostatin acts at five G protein-coupled receptors, sst1-sst5. In mouse ischemic retinas, the over-expression of sst2 (as in sst1 knock-out mice) results in reduction of cell death and glutamate release. Here, we reported that, in wild-type retinas, somatostatin, the multireceptor ligand pasireotide and the sst2 agonist octreotide decreased ischemia-induced cell death and that octreotide also decreased glutamate release. In contrast, cell death was increased by blocking sst2 with cyanamide. In sst2 over-expressing ischemic retinas, somatostatin analogues increased cell death, and octreotide also increased glutamate release. To explain this reversal of the anti-ischemic effect of somatostatin agonists in the presence of sst2 over-expression, we tested sst2 desensitisation due to internalisation or altered receptor function. We observed that: i) sst2 was not internalised, ii) among G protein-coupled receptor kinases (GRKs) and regulators of G protein signalling (RGSs), GRK1 and RGS1 expression increased following ischemia, iii) both GRK1 and RGS1 were down-regulated by octreotide in wild-type ischemic retinas, iv) octreotide down-regulated GRK1 but not RGS1 in sst2 over-expressing ischemic retinas. These results demonstrate that sst2 activation protects against retinal ischemia. However, in the presence of sst2 over-expression sst2 is functionally desensitised by agonists, possibly due to sustained RGS1 levels.
L'articolo è disponibile sul sito dell'editore http://onlinelibrary.wiley.com/
|Appears in Collections:||DISA - Archivio della produzione scientifica|
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