Type-1, but Not Type-5, Metabotropic Glutamate Receptors are Coupled to Polyphosphoinositide Hydrolysis in the Retina

Maria Rosaria Romano, Luisa Di Menna, Pamela Scarselli, Giada Mascio, Michele Madonna, Serena Notartomaso, Aldamaria Puliti, Valeria Bruno, Giuseppe Battaglia, Ferdinando Nicoletti

Research output: Contribution to journalArticle

Abstract

mGlu1 and mGlu5 metabotropic glutamate receptors are expressed in the vertebrate retina, and are co-localized in some retinal neurons. It is believed that both receptors are coupled to polyphosphoinositide (PI) hydrolysis in the retina and their function may diverge in some cells because of a differential engagement of downstream signaling molecules. Here, we show that it is only the mGlu1 receptor that is coupled to PI hydrolysis in the retina. We used either bovine retinal slices or intact mouse retinas challenged with the mixed mGlu1/5 receptor agonist, DHPG. In both models, DHPG-stimulated PI hydrolysis was abrogated by the selective mGlu1 receptor antagonist, JNJ16259685, but was insensitive to the mGlu5 receptor antagonist, MPEP. In addition, the PI response to DHPG was unchanged in the retina of mGlu5(-/-) mice but was abolished in the retina of crv4 mice lacking mGlu1 receptors. Stimulation of the mitogen-activated protein kinase pathway by DHPG in intact mouse retinas were also entirely mediated by mGlu1 receptors. Our data provide the first example of a tissue in which a biochemically detectable PI response is mediated by mGlu1, but not mGlu5, receptors. Hence, bovine retinal slices might be used as a model for the functional screening of mGlu1 receptor ligands. In addition, the mGlu1 receptor caters the potential as a drug target in the experimental treatment of degenerative disorders of the retina.

Original languageEnglish
Pages (from-to)924-32
Number of pages9
JournalNeurochemical Research
Volume41
Issue number4
DOIs
Publication statusPublished - Apr 2016

Keywords

  • Animals
  • Cattle
  • Glycine
  • Hydrolysis
  • Inositol Phosphates
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phosphatidylinositol Phosphates
  • Receptor, Metabotropic Glutamate 5
  • Receptors, Metabotropic Glutamate
  • Resorcinols
  • Retina
  • Signal Transduction
  • Journal Article

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  • Cite this

    Romano, M. R., Di Menna, L., Scarselli, P., Mascio, G., Madonna, M., Notartomaso, S., Puliti, A., Bruno, V., Battaglia, G., & Nicoletti, F. (2016). Type-1, but Not Type-5, Metabotropic Glutamate Receptors are Coupled to Polyphosphoinositide Hydrolysis in the Retina. Neurochemical Research, 41(4), 924-32. https://doi.org/10.1007/s11064-015-1775-y