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

Naunyn-Schmiedeberg's Archives of Pharmacology volume 367, pages 188–192 (2003)Cite this article

Abstract

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.

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Acknowledgements

We wish to thank V. Resta for technical support in the early phase of this work, A. Gazzano for excellent assistance with sst2 KO mouse colony, G. Bresciani for animal care and G. Casini for helpful suggestions and valuable comments on the manuscript. This work was supported by the Italian Board of Education (F06/PB/RS40%) and the European Community (QLG3-1999-00908).

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Affiliations

  1. Dipartimento di Fisiologia e Biochimica "G. Moruzzi", Università di Pisa, Via San Zeno 31, 56127, Pisa, Italy

    Massimo Dal Monte, Cristina Petrucci & Paola Bagnoli

  2. Dipartimento di Farmacologia Clinica e Preclinica, Università di Firenze, Viale Pieraccini 6, 50139, Firenze, Italy

    Andrea Cozzi

  3. Laboratory of Cognitive and Developmental Neuroscience, The Babraham Institute, Babraham, Cambridge, CB2 4AT, UK

    Jeremy P. Allen

Authors
  1. Massimo Dal Monte
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  2. Cristina Petrucci
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  3. Andrea Cozzi
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  4. Jeremy P. Allen
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  5. Paola Bagnoli
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Correspondence to Paola Bagnoli.

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Dal Monte, M., Petrucci, C., Cozzi, A. et al. Somatostatin inhibits potassium-evoked glutamate release by activation of the sst2 somatostatin receptor in the mouse retina. Naunyn-Schmiedeberg's Arch Pharmacol 367, 188–192 (2003). https://doi.org/10.1007/s00210-002-0662-7

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  • DOI: https://doi.org/10.1007/s00210-002-0662-7

Keywords

  • Somatostatin receptor
  • Agonists
  • sst2 knockout
  • Retinal cells
  • Glutamatergic transmission
  • RT-PCR
  • Immunocytochemistry
  • HPLC