title: Different properties of P2X(7) receptor in hippocampal and cortical astrocytes.
abstract: P2X(7) receptor is a ligand-gated ion channel, which can induce the opening of large membrane pores. Here, we provide evidence that the receptor induces pore formation in astrocytes cultured from cortex, but not from the hippocampus. Furthermore, P2X(7) receptor activation promptly induces p38 mitogen-activated protein kinase (MAPK) phosphorylation in cortical but not in hippocampal astrocytes. Given the role of p38 MAPK activation in pore opening, these data suggest that defective coupling of the receptor to the enzyme could occur in hippocampal cultures. The different capabilities of the receptor to open membrane pores cause relevant functional consequences. Upon pore formation, caspase-1 is activated and pro-IL1-beta is cleaved and released extracellularly. The receptor stimulation does not result in interleukin-1beta secretion from hippocampal astrocytes, although the pro-cytokine is present in the cytosol of lipopolysaccharide-primed cultures. These results open the possibility that activation of P2X(7) receptors differently influences the neuroinflammatory processes in distinct brain regions.
authors.affiliation: Department of Medical Pharmacology, CNR Institute of Neuroscience, University of Milan, Via Vanvitelli 32, 20129, Milan, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Bianco
authors.forename: Alessio
authors.initials: A
authors.lastname: Colombo
authors.forename: Laura
authors.initials: L
authors.lastname: Saglietti
authors.forename: Davide
authors.initials: D
authors.lastname: Lecca
authors.forename: Maria Pia
authors.initials: MP
authors.lastname: Abbracchio
authors.forename: Michela
authors.initials: M
authors.lastname: Matteoli
authors.forename: Claudia
authors.initials: C
authors.lastname: Verderio