title: Type-1, but Not Type-5, Metabotropic Glutamate Receptors are Coupled to Polyphosphoinositide Hydrolysis in the Retina.
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.
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
authors.forename: Maria Rosaria
authors.initials: MR
authors.lastname: Romano
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
authors.forename: Luisa
authors.initials: L
authors.lastname: Di Menna
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
authors.forename: Pamela
authors.initials: P
authors.lastname: Scarselli
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
authors.forename: Giada
authors.initials: G
authors.lastname: Mascio
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Madonna
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Notartomaso
authors.affiliation: Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health (DiNOGMI), University of Genoa, Genoa, Italy.|U.O.C. Genetica Medica, Istituto Giannina Gaslini, Genoa, Italy.
authors.forename: Aldamaria
authors.initials: A
authors.lastname: Puliti
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.|Department of Physiology and Pharmacology, University Sapienza, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Bruno
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, IS, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Battaglia
authors.affiliation: I.R.C.C.S. Neuromed, Pozzilli, IS, Italy. ferdinandonicoletti@hotmail.com.|Department of Physiology and Pharmacology, University Sapienza, Rome, Italy. ferdinandonicoletti@hotmail.com.
authors.forename: Ferdinando
authors.initials: F
authors.lastname: Nicoletti
mesh_terms: D000818:Animals; D002417:Cattle; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D006868:Hydrolysis; D007295:Inositol Phosphates / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5 / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D012118:Resorcinols / Q000494:pharmacology; D012160:Retina / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D007295:Inositol Phosphates; D018129:Phosphatidylinositol Phosphates; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D012118:Resorcinols; C104077:metabotropic glutamate receptor type 1; C079215:3,5-dihydroxyphenylglycine; D005998:Glycine
keywords: Polyphosphoinositide hydrolysis; Retina; crv4 mice; mGlu1 receptor