Somatostatin inhibits potassium-evoked glutamate release by activation of the sst2 somatostatin receptor in the mouse retina

Abstract

In the mammalian retina, somatostatin (SRIF-14) acts through distinct receptor subtypes (sst_1–5). Among them, sst₂ has been localized to numerous retinal cells, including photoreceptors and rod bipolar cells (RBCs). The specific role of sst₂ in the retina is largely undetermined. In this study, we characterized retinas of mice with targeted deletion of sst₂ (sst₂ KO) and we investigated functions of sst₂ in respect to its possible modulation of glutamate (GLU) release, as measured by HPLC. In contrast with wild-type (WT) mice, sst₂ mRNA and sst_2A immunoreactivity were no longer detectable in the retina of sst₂ KO mice. In retinal explants of WT mice, SRIF and its analogue octreotide that displays high selectivity for sst₂, similarly reduced the evoked release of GLU without affecting its basal level. In sst₂ KO retinas, SRIF or octreotide did not affect GLU release indicating that they act at sst₂. Unexpectedly, the compound CYN-154806, although introduced as the first potent sst₂ antagonist, reduced the evoked release of GLU with equipotency to SRIF and octreotide. Its inhibitory effect was no longer observed in sst₂ KO retinas, indicating that this substance acts at sst₂ receptors as an agonist. In conclusion, SRIF controls evoked release of GLU through sst₂ receptors and this control may represent part of a mechanism by which SRIF regulates GLU concentration in the retina.