title: The P2X7 receptor as a route for non-exocytotic glutamate release: dependence on the carboxyl tail.
abstract: P2X7 receptors trigger Ca(2+) -dependent exocytotic glutamate release, but also function as a route for non-exocytotic glutamate release from neurons or astrocytes. To gain an insight into the mechanisms involving the P2X7 receptor as a direct pathway for glutamate release, we compared the behavior of a full-length rat P2X7 receptor, a truncated rat P2X7 receptor in which the carboxyl tail had been deleted, a rat P2X7 receptor with the 18-amino acid cysteine-rich motif of the carboxyl tail deleted, and a rat P2X2 receptor, all of which are expressed in HEK293 cells. We found that the P2X7 receptor function as a route for glutamate release was antagonized in a non-competitive way by extracellular Mg(2+) , did not require the recruitment of pore-forming molecules, and was dependent on the carboxyl tail. Indeed, the truncated P2X7 receptor and the P2X7 receptor with the deleted cysteine-rich motif both lost their function as a pathway for glutamate release, while still evoking intracellular Ca(2+) elevation. No glutamate efflux was observed through the P2X2 receptor. Notably, HEK293 cells (lacking the machinery for Ca(2+) -dependent exocytosis), when transfected with P2X7 receptors, appear to be a suitable model for investigating the P2X7 receptor as a route for non-exocytotic glutamate efflux.
authors.affiliation: Department of Pharmacy, University of Genova, Genova, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Cervetto
authors.forename: Susanna
authors.initials: S
authors.lastname: Alloisio
authors.forename: Daniela
authors.initials: D
authors.lastname: Frattaroli
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Mazzotta
authors.forename: Marco
authors.initials: M
authors.lastname: Milanese
authors.forename: Paola
authors.initials: P
authors.lastname: Gavazzo
authors.forename: Mario
authors.initials: M
authors.lastname: Passalacqua
authors.forename: Mario
authors.initials: M
authors.lastname: Nobile
authors.forename: Guido
authors.initials: G
authors.lastname: Maura
authors.forename: Manuela
authors.initials: M
authors.lastname: Marcoli
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D003545:Cysteine / Q000172:deficiency; D005089:Exocytosis / Q000235:genetics; D018698:Glutamic Acid / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D051381:Rats; D058486:Receptors, Purinergic P2X7 / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D058486:Receptors, Purinergic P2X7; D018698:Glutamic Acid; C033901:3'-O-(4-benzoyl)benzoyladenosine 5'-triphosphate; D000255:Adenosine Triphosphate; D003545:Cysteine; D002118:Calcium