G-Protein Coupled Receptor-Evoked Glutamate Exocytosis from Astrocytes: Role of Prostaglandins. (16th January 2014)

• Record Type: Journal Article
• Authors: Cali, Corrado; Lopatar, Jan; Petrelli, Francesco; Pucci, Luca; Bezzi, Paola
• Other Names: Jones Emma Victoria Academic Editor.
• Is Part Of: Neural plasticity. Volume 2014(2014)
• Publication Date: 2014-01-16
• Subjects: Neuroplasticity -- Periodicals; 612.82
• DOI: 10.1155/2014/254574
• Languages: English
• ISSNs: 2090-5904

Abstract

Abstract : Astrocytes are highly secretory cells, participating in rapid brain communication by releasing glutamate. Recent evidences have suggested that this process is largely mediated by Ca 2+ -dependent regulated exocytosis of VGLUT-positive vesicles. Here by taking advantage of VGLUT1-pHluorin and TIRF illumination, we characterized mechanisms of glutamate exocytosis evoked by endogenous transmitters (glutamate and ATP), which are known to stimulate Ca 2+ elevations in astrocytes. At first we characterized the VGLUT1-pHluorin expressing vesicles and found that VGLUT1-positive vesicles were a specific population of small synaptic-like microvesicles containing glutamate but which do not express VGLUT2. Endogenous mediators evoked a burst of exocytosis through activation of G-protein coupled receptors. Subsequent glutamate exocytosis was reduced by about 80% upon pharmacological blockade of the prostaglandin-forming enzyme, cyclooxygenase. On the other hand, receptor stimulation was accompanied by extracellular release of prostaglandin E2 (PGE2 ). Interestingly, administration of exogenous PGE2 produced per se rapid, store-dependent burst exocytosis of glutamatergic vesicles in astrocytes. Finally, when PGE2 -neutralizing antibody was added to cell medium, transmitter-evoked exocytosis was again significantly reduced (by about 50%). Overall these data indicate that cyclooxygenase products are responsible for a major component of glutamate exocytosis in astrocytes and that large part of such component is sustained by autocrine/paracrine action of PGE2 .