title: Changes in phosphoinositide signalling activity and levels of the alpha subunit of G(q/11) protein in rat brain induced by E-5842, a sigma(1) receptor ligand and potential atypical antipsychotic.
abstract: Changes in the phosphoinositide (PPI) signal transduction system induced by E-5842, a new sigma(1) (sigma(1)) receptor ligand and potential atypical antipsychotic, were studied in the rat frontal cortex, hippocampus and striatum. Acute treatment with E-5842 increased phospholipase C (PLC) activity in the striatum and the hippocampus. Chronic treatment with E-5842 induced an increase in the activity of PLC in the frontal cortex and the striatum. Similar up-regulation of the activity of the enzyme was also observed in rat frontal cortex membranes in presence of GTPgammaS. After chronic treatment with E-5842, it was also observed a significant increase of the immunoreactivity levels of G(q/11)alpha in the frontal cortex. Our results suggest that part of the antipsychotic effects of E-5842 could be related to the regulation of the PPI signal transduction pathway, especially after a prolonged treatment.
authors.affiliation: Department of Neuropharmacology, Research Center, Laboratorio Esteve, S.A., Verge de Montserrat, 22, 08041, Barcelona, Spain.
authors.forename: G
authors.initials: G
authors.lastname: Romero
authors.forename: M P
authors.initials: MP
authors.lastname: Pérez
authors.forename: A
authors.initials: A
authors.lastname: Carceller
authors.forename: X
authors.initials: X
authors.lastname: Monroy
authors.forename: A J
authors.initials: AJ
authors.lastname: Farré
authors.forename: X
authors.initials: X
authors.lastname: Guitart
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017480:Receptors, sigma / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D014230:Triazoles / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000187:drug effects* / Q000378:metabolism; D000097605:Sigma-1 Receptor
chemical_list: D014150:Antipsychotic Agents; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019204:GTP-Binding Proteins; D010716:Phosphatidylinositols; D011725:Pyridines; D017480:Receptors, sigma; D014230:Triazoles; D010738:Type C Phospholipases; D000097605:Sigma-1 Receptor; C117757:E 5842