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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
Martini, Davide
Ristori, Chiara
Catalani, Elisabetta
Timperio, Anna Maria
Bagnoli, Paola
Casini, Giovanni
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
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.
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ISSN: 0022-3042
DOI: 10.1111/j.1471-4159.2008.05556.x
Appears in Collections:DISA - Archivio della produzione scientifica

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