Somatostatin inhibits potassium-evoked glutamate release by activation of the sst2 somatostatin receptor in the mouse retina
2003
In the mammalian retina, somatostatin (SRIF-14) acts through distinct receptor subtypes (sst1–5). 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 sst2A 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.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
33
References
48
Citations
NaN
KQI