Nown. It has long been known that the ER membrane, k Can different classes of receptor tyrosine kinases, such as receptors transactivate the epidermal growth factor and type I insulin Like growth factor receptors. In addition, this mechanism is the transactivation of metabotropic glutamate receptors, the G-protein-coupled receptors are eight subtypes of mGlu extended receptors has been described in three groups on its amino Acid sequence, pharmacological profile and transduction pathways divided. Group I subtypes are Gq coupled, and their activation leads to hydrolysis with subsequent Final formation of inositol 1,4,5-triphosphate, and diacylglycerol polyphosphoinositide. mGlu1 and mGlu5 receptors can activate MAPK and also PtdIns 3 K, and group II receptor subtypes of group III are all with Gi / GB proteins coupled. A series of elegant studies have shown that ER-membrane receptors mGlu1 receptors transactivate the hypothalamus. For example, mGlu1 receptor transactivation by ER in hypothalamic astrocytes leads to the synthesis of neuro-progesterone, which is necessary for the thrust of estradiol induced ovulatory luteinizing hormone. In neurons of the hypothalamus, as evidenced by the stimulation of ER Estradiol son on the internalization of mGlu1 receptors ER and that both receptors interact in neurons also. In contrast, GPR30 does not couple to appear with mGlu1 receptor and the receptor in the fast-VER Santander intracellular ligands Involved re Ca2 signaling in astrocytes. mGlu1 receptors are linked to mechanisms of neurodegeneration / neuroprotection and may verst RKT or attenuated cht neuronal death in dependence dependence of the TGF-beta cellular Ren and context of the experimental paradigm of neurodegeneration. We now report that activation of either ER or mGlu1 receptor protects cortical neurons against the toxicity of t amylo of the substance Of receptors and that the two mutually survive in supporting neuronal. This is the first evidence that mGlu1 receptors ER and interact in cortical neurons.
Materials and Methods Drugs and reagents. 17 estradiol, 1,3,5 tris four propyl 1H-pyrazole, diarylpropionitrile and fulvestrant was dissolved in ethanol gel St. Methanone and 3.5 dihydroxyphenylglycine, Tocris Cookson Ltd. of whether purchased in dimethyl sulfoxide gel St, 10 2 chlorophenoxazine hydrochloride and were 2-6-methylpyridine in water gel St 17E2 and BSA conjugate was dissolved St in 50% ethanol. Amylo From peptidesA1 andA25 42 35 were obtained from Bachem. A1 42 in dimethyl sulfoxide in a anf Nglichen concentration of 5 mM gel St w While L25 is 35 in water at a anf Nglichen concentration of 2.5 mM solubilized. All Stamml Solutions were diluted in culture medium, where appropriate prior to use. Inositol was purchased from GE Healthcare. Cell culture materials and all plastics, unless otherwise specified, were obtained from Invitrogen and Nalge Nunc International. All drugs were used at concentrations in the literature to be effective in the cell. In the case of DHPG and 17E2, concentration-response studies were carried out in a first phase, so that the choice of the concentration to be used. Prim Re cell cultures. All experiments on animals were in accordance with the guidelines for the control of the Italian and Europ Conducted European Union for financial support.