| First Author | Cervia D | Year | 2008 |
| Journal | J Neurochem | Volume | 106 |
| Issue | 5 | Pages | 2224-35 |
| PubMed ID | 18624922 | Mgi Jnum | J:138851 |
| Mgi Id | MGI:3806723 | Doi | 10.1111/j.1471-4159.2008.05556.x |
| Citation | Cervia D, et al. (2008) Modulation of the neuronal response to ischaemia by somatostatin analogues in wild-type and knock-out mouse retinas. J Neurochem 106(5):2224-35 |
| abstractText | Somatostatin acts at five G protein-coupled receptors, sst(1)-sst(5). In mouse ischaemic retinas, the over-expression of sst(2) (as in sst(1) knock-out mice) results in the reduction of cell death and glutamate release. In this study, we reported that, in wild-type retinas, somatostatin, the multireceptor ligand pasireotide and the sst(2) agonist octreotide decreased ischaemia-induced cell death and that octreotide also decreased glutamate release. In contrast, cell death was increased by blocking sst(2) with cyanamide. In sst(2) over-expressing ischaemic retinas, somatostatin analogues increased cell death, and octreotide also increased glutamate release. To explain this reversal of the anti-ischaemic effect of somatostatin agonists in the presence of sst(2) over-expression, we tested sst(2) desensitisation because of internalisation or altered receptor function. We observed that (i) sst(2) was not internalised, (ii) among G protein-coupled receptor kinases (GRKs) and regulators of G protein signalling (RGSs), GRK1 and RGS1 expression increased following ischaemia, (iii) both GRK1 and RGS1 were down-regulated by octreotide in wild-type ischaemic retinas, (iv) octreotide down-regulated GRK1 but not RGS1 in sst(2) over-expressing ischaemic retinas. These results demonstrate that sst(2) activation protects against retinal ischaemia. However, in the presence of sst(2) over-expression sst(2) is functionally desensitised by agonists, possibly because of sustained RGS1 levels. |
