星狀神經膠細胞 (Astrocyte) 具有一個重要的功能，就是將突觸間的麩氨酸 (glutamate) 清除，目的為了避免過多的麩氨酸造成興奮性神經毒性 (excitatory neurotoxicity)，而這些回收回來的麩氨酸就是透過麩氨合成酵素 (Glutamine Synthetase) 這個酵素轉變成為麩醯胺酸(glutamine)。目前的研究已經證實麩氨合成酵素在一些神經退化性疾病或腦部受傷缺氧所引起的神經毒性中扮演一個重要的角色。但是在腦部受傷時，調控麩氨合成酵素的分子機轉仍不清楚。
從目前的研究我們發現，第二型星狀膠細胞--RBA-2，在正常的細胞培養情況下，麩氨合成酵素的活性及蛋白質表現量遠比C6神經膠瘤細胞株和IA1g1星狀神經膠細胞株多。另外也發現外加麩氨酸會增加麩氨合成酵素的活性和蛋白質的表現。在高濃度的ATP（1mM）刺激之下，發現隨時間的增加，麩氨合成酵素的活性和蛋白質的表現都會下降。為了探討P2X7接受器的活化是否有參與此訊號傳遞，我使用了P2X7接受器的agonist，BzATP和antagonist，oATP等藥物觀察是否影響ATP對麩氨合成酵素的作用，結果發現oATP抑制了ATP和BzATP引起的麩氨合成酵素蛋白質表現的下降。因為已經知道活化P2X7接受器後會造成細胞外鈣離子流入細胞內以及PKC的活化，結果也發現在沒有鈣離子的存在下，ATP對麩氨合成酵素蛋白質的表現的作用受到抑制;加入PKC的抑制劑也會抑制ATP對麩氨合成酵素蛋白質表現的作用。另外，為了探討c-Jun是否有參與在這個訊號傳遞的過程中，我使用了活化c-Jun的kinase─JNK (c-Jun N-terminal kinase) 的抑制劑--- JNK inhibitor Ⅰ，發現處理JNK inhibitor Ⅰ後無法完全抑制ATP對麩氨合成酵素的作用，表示c-Jun不參與ATP所造成的麩氨合成酵素活性和蛋白質表現的下降。
綜合以上的結果，我們發現RBA-2有豐富的麩氨合成酵素，ATP使麩氨合成酵素的活性和蛋白質的表現下降，是需要透過P2X7接受器的活化，以及細胞外鈣離子流入細胞內，也證實PKC的活化有參與其中。

One of the important physiological functions of astrocyte is to metabolize excitatory neurotransmitter, glutamate. Therefore, astrocytes play a key role in protection of neurons from ischemia-induced excitatory toxicity through taking up excess glutamate and converting it to glutamine via the enzyme glutamine synthetase. Recent studies have demonstrated that glutamine synthetase may be a critical factor in the neurotoxicity produced after CNS injury or ischemia. However, the molecular mechanisms that modulate GS expression in astrocytes after CNS injury are not clear.
The study investigates the effect of ATP on glutamine synthetase activity and protein expression of RBA-2 type 2 astrocytes. RBA-2 astrocytes expressed abundant glutamine synthetase in the basal culture condition as compared with C6 astrocytoma cells and IA1g1 type-1 astrocytes. Exogenous glutamate induced a dose-dependent increase in GS activity and protein expression. Treating the cells with ATP (1 mM) caused a significant decrease on GS activity and protein expression . Because RBA-2 astrocytes were known to express P2X7 receptor, and activation of P2X7 receptor stimulated Ca2+ influx and protein kinase C , we elucidate whether activation of P2X7 receptors and the signal mechanisms are involved in the ATP-altered GS expression. The P2X7 receptor selective antagonist, oATP ( 100 μM ) inhibited the ATP- and BzATP-reduced GS expression. Treatment of cells with Ca+2 free buffer inhibited the ATP- and BzATP-reduced GS expression. In addition, treatment of cells with PKC inhibitors GF109203X and GÖ6976 rescued the ATP- and BzATP-reduced GS expression. Because c-jun was known to mediate glutamine synthetase regulation, RBA-2 was treated with JNK inhibitor Ⅰ. The result showed that JNK inhibitor Ⅰcan’t inhibited the effect of ATP on the glutamine synthetase expression.
Take together, we have demonstrated that RBA-2 expressed abundant GS, glutamate enhanced GS expression, and exposure of astrocyte to ATP altered GS activity and protein expression. The decrease in GS protein expression is dependent on PKC activation via P2X7 receptors.

頁次
英文縮寫對照表.................................1
中文摘要.......................................2
英文摘要.......................................4
序論...........................................6
實驗材料與方法.................................13
結果...........................................20
討論...........................................27
參考文獻.......................................33
圖表...........................................44

Reference List
1. Abbracchio,M.P. and Burnstock,G. (1994). Purinoceptors: are there families of P2X and P2Y purinoceptors? Pharmacol.Ther. 64, 445-475.
2. Allen,J.W., Mutkus,L.A., and Aschner,M. (2001). Mercuric chloride, but not methylmercury, inhibits glutamine synthetase activity in primary cultures of cortical astrocytes. Brain Res. 891, 148-157.
3. Ballerini,P., Rathbone,M.P., Di Iorio,P., Renzetti,A., Giuliani,P., D''Alimonte,I., Trubiani,O., Caciagli,F., and Ciccarelli,R. (1996). Rat astroglial P2Z (P2X7) receptors regulate intracellular calcium and purine release. Neuroreport 7, 2533-2537.
4. Baranano,D.E., Ferris,C.D., and Snyder,S.H. (2001). Atypical neural messengers. Trends Neurosci. 24, 99-106.
5. Barr,R.K., Kendrick,T.S., and Bogoyevitch,M.A. (2002). Identification of the critical features of a small peptide inhibitor of JNK activity. J.Biol.Chem. 277, 10987-10997.
6. Belin,M.F., Didier-Bazes,M., Akaoka,H., Hardin-Pouzet,H., Bernard,A., and Giraudon,P. (1997). Changes in astrocytic glutamate catabolism enzymes following neuronal degeneration or viral infection. Glia 21, 154-161.
7. Ben Dror,I., Havazelet,N., and Vardimon,L. (1993). Developmental control of glucocorticoid receptor transcriptional activity in embryonic retina. Proc.Natl.Acad.Sci.U.S.A 90, 1117-1121.
8. Benjamin,A.M. and Quastel,J.H. (1975). Metabolism of amino acids and ammonia in rat brain cortex slices in vitro: a possible role of ammonia in brain function. J.Neurochem. 25, 197-206.
9. Berko-Flint,Y., Levkowitz,G., and Vardimon,L. (1994). Involvement of c-Jun in the control of glucocorticoid receptor transcriptional activity during development of chicken retinal tissue. EMBO J. 13, 646-654.
10. Bezzi,P., Domercq,M., Vesce,S., and Volterra,A. (2001). Neuron-astrocyte cross-talk during synaptic transmission: physiological and neuropathological implications. Prog.Brain Res. 132, 255-265.
11. Bezzi,P. and Volterra,A. (2001). A neuron-glia signalling network in the active brain. Curr.Opin.Neurobiol. 11, 387-394.
12. Boksha,I.S., Schonfeld,H.J., Langen,H., Muller,F., Tereshkina,E.B., and Burbaeva,G.S. (2002). Glutamine synthetase isolated from human brain: octameric structure and homology of partial primary structure with human liver glutamine synthetase. Biochemistry (Mosc.) 67, 1012-1020.
13. Bradford,M.M. (1976). A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal.Biochem. 72, 248-254.
14. Buell,G., Collo,G., and Rassendren,F. (1996). P2X receptors: an emerging channel family. Eur.J.Neurosci. 8, 2221-2228.
15. Buisman,H.P., Steinberg,T.H., Fischbarg,J., Silverstein,S.C., Vogelzang,S.A., Ince,C., Ypey,D.L., and Leijh,P.C. (1988). Extracellular ATP induces a large nonselective conductance in macrophage plasma membranes. Proc.Natl.Acad.Sci.U.S.A 85, 7988-7992.
16. Burnstock,G. (1972). Purinergic nerves. Pharmacol.Rev. 24, 509-581.
17. Burnstock,G. (1988). Sympathetic purinergic transmission in small blood vessels. Trends Pharmacol.Sci. 9, 116-117.
18. Burnstock,G. (1990). Overview. Purinergic mechanisms. Ann.N.Y.Acad.Sci. 603, 1-17.
19. Burnstock,G. (1997). The past, present and future of purine nucleotides as signalling molecules. Neuropharmacology 36, 1127-1139.
20. Burnstock,G. and Kennedy,C. (1986). A dual function for adenosine 5''-triphosphate in the regulation of vascular tone. Excitatory cotransmitter with noradrenaline from perivascular nerves and locally released inhibitory intravascular agent. Circ.Res. 58, 319-330.
21. Cammer,W. (1990). Glutamine synthetase in the central nervous system is not confined to astrocytes. J.Neuroimmunol. 26, 173-178.
22. Choi,D.W. (1988). Glutamate neurotoxicity and diseases of the nervous system. Neuron 1, 623-634.
23. Cohen,D.M. (1997). Inhibition of glutamine synthetase induces critical energy threshold for neuronal survival. Ann.N.Y.Acad.Sci. 826, 456-460.
24. Cotrina,M.L., Lin,J.H., Lopez-Garcia,J.C., Naus,C.C., and Nedergaard,M. (2000). ATP-mediated glia signaling. J.Neurosci. 20, 2835-2844.
25. Coutinho-Silva,R., Persechini,P.M., Bisaggio,R.D., Perfettini,J.L., Neto,A.C., Kanellopoulos,J.M., Motta-Ly,I., Dautry-Varsat,A., and Ojcius,D.M. (1999). P2Z/P2X7 receptor-dependent apoptosis of dendritic cells. Am.J.Physiol 276, C1139-C1147.
26. Cunha,R.A. and Ribeiro,J.A. (2000). Purinergic modulation of [(3)H]GABA release from rat hippocampal nerve terminals. Neuropharmacology 39, 1156-1167.
27. Danbolt,N.C. (1994). The high affinity uptake system for excitatory amino acids in the brain. Prog.Neurobiol. 44, 377-396.
28. DeMarco,V., McCain,M.D., Strauss,D., Chakrabarti,R., and Neu,J. (1997). Characterization of glutamine synthetase transcript, protein, and enzyme activity in the human placenta. Placenta 18, 541-545.
29. Di Virgilio,F., Sanz,J.M., Chiozzi,P., and Falzoni,S. (1999). The P2Z/P2X7 receptor of microglial cells: a novel immunomodulatory receptor. Prog.Brain Res. 120, 355-368.
30. Dickens,M., Rogers,J.S., Cavanagh,J., Raitano,A., Xia,Z., Halpern,J.R., Greenberg,M.E., Sawyers,C.L., and Davis,R.J. (1997). A cytoplasmic inhibitor of the JNK signal transduction pathway. Science 277, 693-696.
31. Engle,M.J. and Volpe,J.J. (1990). Glutamine synthetase activity of developing astrocytes is inhibited in vitro by very low concentrations of lead. Brain Res.Dev.Brain Res. 55, 283-287.
32. Ferrari,D., Chiozzi,P., Falzoni,S., Hanau,S., and Di Virgilio,F. (1997). Purinergic modulation of interleukin-1 beta release from microglial cells stimulated with bacterial endotoxin. J.Exp.Med. 185, 579-582.
33. Fields,R.D. and Stevens-Graham,B. (2002). New insights into neuron-glia communication. Science 298, 556-562.
34. Fleischer-Lambropoulos,E., Kazazoglou,T., Geladopoulos,T., Kentroti,S., Stefanis,C., and Vernadakis,A. (1996). Stimulation of glutamine synthetase activity by excitatory amino acids in astrocyte cultures derived from aged mouse cerebral hemispheres may be associated with non-N-methyl-D-aspartate receptor activation. Int.J.Dev.Neurosci. 14, 523-530.
35. Fonnum,F. (1984). Glutamate: a neurotransmitter in mammalian brain. J.Neurochem. 42, 1-11.
36. Fredholm,B.B., Abbracchio,M.P., Burnstock,G., Daly,J.W., Harden,T.K., Jacobson,K.A., Leff,P., and Williams,M. (1994). Nomenclature and classification of purinoceptors. Pharmacol.Rev. 46, 143-156.
37. Gordon,J.L. (1986). Extracellular ATP: effects, sources and fate. Biochem.J. 233, 309-319.
38. Gorovits,R., Avidan,N., Avisar,N., Shaked,I., and Vardimon,L. (1997). Glutamine synthetase protects against neuronal degeneration in injured retinal tissue. Proc.Natl.Acad.Sci.U.S.A 94, 7024-7029.
39. Gorovits,R., Yakir,A., Fox,L.E., and Vardimon,L. (1996). Hormonal and non-hormonal regulation of glutamine synthetase in the developing neural retina. Brain Res.Mol.Brain Res. 43, 321-329.
40. Gunnersen,D. and Haley,B. (1992). Detection of glutamine synthetase in the cerebrospinal fluid of Alzheimer diseased patients: a potential diagnostic biochemical marker. Proc.Natl.Acad.Sci.U.S.A 89, 11949-11953.
41. Guthrie,P.B., Knappenberger,J., Segal,M., Bennett,M.V., Charles,A.C., and Kater,S.B. (1999). ATP released from astrocytes mediates glial calcium waves. J.Neurosci. 19, 520-528.
42. Harden,T.K., Boyer,J.L., and Nicholas,R.A. (1995). P2-purinergic receptors: subtype-associated signaling responses and structure. Annu.Rev.Pharmacol.Toxicol. 35, 541-579.
43. Hertz,L., Dringen,R., Schousboe,A., and Robinson,S.R. (1999). Astrocytes: glutamate producers for neurons. J.Neurosci.Res. 57, 417-428.
44. Hung,A.C. and Sun,S.H. (2002). The P2X(7) receptor-mediated phospholipase D activation is regulated by both PKC-dependent and PKC-independent pathways in a rat brain-derived Type-2 astrocyte cell line, RBA-2. Cell Signal. 14, 83-92.
45. Jackson,M.J., Zielke,H.R., and Max,S.R. (1995). Effect of dibutyryl cyclic AMP and dexamethasone on glutamine synthetase gene expression in rat astrocytes in culture. Neurochem.Res. 20, 201-207.
46. James,G. and Butt,A.M. (2002). P2Y and P2X purinoceptor mediated Ca(2+) signalling in glial cell pathology in the central nervous system. Eur.J.Pharmacol. 447, 247-260.
47. Jonat,C., Rahmsdorf,H.J., Park,K.K., Cato,A.C., Gebel,S., Ponta,H., and Herrlich,P. (1990). Antitumor promotion and antiinflammation: down-modulation of AP-1 (Fos/Jun) activity by glucocorticoid hormone. Cell 62, 1189-1204.
48. Ju,Y.J., Wang,C.M., Hung,A.C., Lo,J.C., Lin,H.J., and Sun,S.H. (2003). Endothelin-1 stimulated capacitative Ca(2+) entry through ET(A) receptors of a rat brain-derived type-1 astrocyte cell line, IA-1g1. Cell Signal. 15, 197-207.
49. Juurlink,B.H. and Hertz,L. (1991). Establishment of highly enriched type-2 astrocyte cultures and quantitative determination of intense glutamine synthetase activity in these cells. J.Neurosci.Res. 30, 531-539.
50. Kamei,Y., Xu,L., Heinzel,T., Torchia,J., Kurokawa,R., Gloss,B., Lin,S.C., Heyman,R.A., Rose,D.W., Glass,C.K., and Rosenfeld,M.G. (1996). A CBP integrator complex mediates transcriptional activation and AP-1 inhibition by nuclear receptors. Cell 85, 403-414.
51. Kapoor,J.R. and Sladek,C.D. (2000). Purinergic and adrenergic agonists synergize in stimulating vasopressin and oxytocin release. J.Neurosci. 20, 8868-8875.
52. King,B.F., Townsend-Nicholson,A., and Burnstock,G. (1998). Metabotropic receptors for ATP and UTP: exploring the correspondence between native and recombinant nucleotide receptors. Trends Pharmacol.Sci. 19, 506-514.
53. Kruchkova,Y., Ben Dror,I., Herschkovitz,A., David,M., Yayon,A., and Vardimon,L. (2001). Basic fibroblast growth factor: a potential inhibitor of glutamine synthetase expression in injured neural tissue. J.Neurochem. 77, 1641-1649.
54. Krugel,U., Kittner,H., and Illes,P. (1999). Adenosine 5''-triphosphate-induced dopamine release in the rat nucleus accumbens in vivo. Neurosci.Lett. 265, 49-52.
55. Labow,B.I., Souba,W.W., and Abcouwer,S.F. (1999). Glutamine synthetase expression in muscle is regulated by transcriptional and posttranscriptional mechanisms. Am.J.Physiol 276, E1136-E1145.
56. Labrakakis,C., Gerstner,E., and MacDermott,A.B. (2000). Adenosine triphosphate-evoked currents in cultured dorsal root ganglion neurons obtained from rat embryos: desensitization kinetics and modulation of glutamate release. Neuroscience 101, 1117-1126.
57. Le Feuvre,R.A., Brough,D., Iwakura,Y., Takeda,K., and Rothwell,N.J. (2002). Priming of macrophages with lipopolysaccharide potentiates P2X7-mediated cell death via a caspase-1-dependent mechanism, independently of cytokine production. J.Biol.Chem. 277, 3210-3218.
58. Levine,R.L., Oliver,C.N., Fulks,R.M., and Stadtman,E.R. (1981). Turnover of bacterial glutamine synthetase: oxidative inactivation precedes proteolysis. Proc.Natl.Acad.Sci.U.S.A 78, 2120-2124.
59. Lewis,T.S., Shapiro,P.S., and Ahn,N.G. (1998). Signal transduction through MAP kinase cascades. Adv.Cancer Res. 74, 49-139.
60. Liaw,S.H., Villafranca,J.J., and Eisenberg,D. (1993). A model for oxidative modification of glutamine synthetase, based on crystal structures of mutant H269N and the oxidized enzyme. Biochemistry 32, 7999-8003.
61. Martiny-Baron,G., Kazanietz,M.G., Mischak,H., Blumberg,P.M., Kochs,G., Hug,H., Marme,D., and Schachtele,C. (1993). Selective inhibition of protein kinase C isozymes by the indolocarbazole Go 6976. J.Biol.Chem. 268, 9194-9197.
62. Mayer,M.L. and Westbrook,G.L. (1987). The physiology of excitatory amino acids in the vertebrate central nervous system. Prog.Neurobiol. 28, 197-276.
63. Mearow,K.M., Mill,J.F., and Freese,E. (1990). Neuron-glial interactions involved in the regulation of glutamine synthetase. Glia 3, 385-392.
64. Meldrum,B. and Garthwaite,J. (1990). Excitatory amino acid neurotoxicity and neurodegenerative disease. Trends Pharmacol.Sci. 11, 379-387.
65. Nakamura,K. and Stadtman,E.R. (1984). Oxidative inactivation of glutamine synthetase subunits. Proc.Natl.Acad.Sci.U.S.A 81, 2011-2015.
66. Neary,J.T., van Breemen,C., Forster,E., Norenberg,L.O., and Norenberg,M.D. (1988). ATP stimulates calcium influx in primary astrocyte cultures. Biochem.Biophys.Res.Commun. 157, 1410-1416.
67. Newton,A.C. (1995). Protein kinase C: structure, function, and regulation. J.Biol.Chem. 270, 28495-28498.
68. Nishizuka,Y. (1992). Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science 258, 607-614.
69. Nishizuka,Y. (1995). Protein kinase C and lipid signaling for sustained cellular responses. FASEB J. 9, 484-496.
70. Norenberg,M.D. and Martinez-Hernandez,A. (1979). Fine structural localization of glutamine synthetase in astrocytes of rat brain. Brain Res. 161, 303-310.
71. Nunez,L., Villalobos,C., and Frawley,L.S. (1997). Extracellular ATP as an autocrine/paracrine regulator of prolactin release. Am.J.Physiol 272, E1117-E1123.
72. Oliver,C.N., Starke-Reed,P.E., Stadtman,E.R., Liu,G.J., Carney,J.M., and Floyd,R.A. (1990). Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain. Proc.Natl.Acad.Sci.U.S.A 87, 5144-5147.
73. Raff,M.C., Abney,E.R., Cohen,J., Lindsay,R., and Noble,M. (1983). Two types of astrocytes in cultures of developing rat white matter: differences in morphology, surface gangliosides, and growth characteristics. J.Neurosci. 3, 1289-1300.
74. Raff,M.C., Abney,E.R., and Miller,R.H. (1984). Two glial cell lineages diverge prenatally in rat optic nerve. Dev.Biol. 106, 53-60.
75. Rassendren,F., Buell,G.N., Virginio,C., Collo,G., North,R.A., and Surprenant,A. (1997). The permeabilizing ATP receptor, P2X7. Cloning and expression of a human cDNA. J.Biol.Chem. 272, 5482-5486.
76. Rieger,F., Faivre-Bauman,A., Benda,P., and Vigny,M. (1976). Molecular forms of acetylcholinesterase: their de novo synthesis in mouse neuroblastoma cells. J.Neurochem. 27, 1059-1063.
77. Ross,C.D. and Godfrey,D.A. (1987). Distribution of activities of aspartate aminotransferase isoenzymes and malate dehydrogenase in guinea pig retinal layers. J.Histochem.Cytochem. 35, 669-674.
78. Rothman,S.M. and Olney,J.W. (1986). Glutamate and the pathophysiology of hypoxic--ischemic brain damage. Ann.Neurol. 19, 105-111.
79. Rothstein,J.D., Dykes-Hoberg,M., Pardo,C.A., Bristol,L.A., Jin,L., Kuncl,R.W., Kanai,Y., Hediger,M.A., Wang,Y., Schielke,J.P., and Welty,D.F. (1996). Knockout of glutamate transporters reveals a major role for astroglial transport in excitotoxicity and clearance of glutamate. Neuron 16, 675-686.
80. Sawynok,J., Downie,J.W., Reid,A.R., Cahill,C.M., and White,T.D. (1993). ATP release from dorsal spinal cord synaptosomes: characterization and neuronal origin. Brain Res. 610, 32-38.
81. Schousboe,A., Hertz,L., Svenneby,G., and Kvamme,E. (1979). Phosphate activated glutaminase activity and glutamine uptake in primary cultures of astrocytes. J.Neurochem. 32, 943-950.
82. Schousboe,A., Westergaard,N., Sonnewald,U., Petersen,S.B., Huang,R., Peng,L., and Hertz,L. (1993). Glutamate and glutamine metabolism and compartmentation in astrocytes. Dev.Neurosci. 15, 359-366.
83. Schousboe,A., Westergaard,N., Sonnewald,U., Petersen,S.B., Yu,A.C., and Hertz,L. (1992). Regulatory role of astrocytes for neuronal biosynthesis and homeostasis of glutamate and GABA. Prog.Brain Res. 94, 199-211.
84. Schule,R., Rangarajan,P., Kliewer,S., Ransone,L.J., Bolado,J., Yang,N., Verma,I.M., and Evans,R.M. (1990). Functional antagonism between oncoprotein c-Jun and the glucocorticoid receptor. Cell 62, 1217-1226.
85. Schulze-Lohoff,E., Hugo,C., Rost,S., Arnold,S., Gruber,A., Brune,B., and Sterzel,R.B. (1998). Extracellular ATP causes apoptosis and necrosis of cultured mesangial cells via P2Z/P2X7 receptors. Am.J.Physiol 275, F962-F971.
86. Sierra,E.M., Rowles,T.K., Martin,J., Bratton,G.R., Womac,C., and Tiffany-Castiglioni,E. (1989). Low level lead neurotoxicity in a pregnant guinea pigs model: neuroglial enzyme activities and brain trace metal concentrations. Toxicology 59, 81-96.
87. Sierra,E.M. and Tiffany-Castiglioni,E. (1991). Reduction of glutamine synthetase activity in astroglia exposed in culture to low levels of inorganic lead. Toxicology 65, 295-304.
88. Simon,J., Webb,T.E., King,B.F., Burnstock,G., and Barnard,E.A. (1995). Characterisation of a recombinant P2Y purinoceptor. Eur.J.Pharmacol. 291, 281-289.
89. Sun,S.H., Lin,L.B., Hung,A.C., and Kuo,J.S. (1999). ATP-stimulated Ca2+ influx and phospholipase D activities of a rat brain-derived type-2 astrocyte cell line, RBA-2, are mediated through P2X7 receptors. J.Neurochem. 73, 334-343.
90. Surprenant,A., Rassendren,F., Kawashima,E., North,R.A., and Buell,G. (1996). The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272, 735-738.
91. Svendsen,C.N. (2002). The amazing astrocyte. Nature 417, 29-32.
92. Tansey,F.A., Farooq,M., and Cammer,W. (1991). Glutamine synthetase in oligodendrocytes and astrocytes: new biochemical and immunocytochemical evidence. J.Neurochem. 56, 266-272.
93. Tereshkina,E.B., Bokina,I.S., Savushkina,O.K., and Burbaeva,G.S. (2000). [Glutamine synthetase and related protein in the frontal cortex in schizophrenia]. Zh.Nevrol.Psikhiatr.Im S.S.Korsakova 100, 51-52.
94. Tholey,G., Sena,A.H., and Ledig,M. (1986). Specific insulin-mediated regulation of glutamine synthetase in cultured chick astroglial cells. J.Neurochem. 47, 1490-1492.
95. Trendelenburg,A.U. and Bultmann,R. (2000). P2 receptor-mediated inhibition of dopamine release in rat neostriatum. Neuroscience 96, 249-252.
96. Troadec,J.D., Thirion,S., Nicaise,G., Lemos,J.R., and Dayanithi,G. (1998). ATP-evoked increases in [Ca2+]i and peptide release from rat isolated neurohypophysial terminals via a P2X2 purinoceptor. J.Physiol 511 ( Pt 1), 89-103.
97. Ullian,E.M., Sapperstein,S.K., Christopherson,K.S., and Barres,B.A. (2001). Control of synapse number by glia. Science 291, 657-661.
98. Vardimon,L., Fox,L.L., Degenstein,L., and Moscona,A.A. (1988). Cell contacts are required for induction by cortisol of glutamine synthetase gene transcription in the retina. Proc.Natl.Acad.Sci.U.S.A 85, 5981-5985.
99. Vizi,E.S. and Knoll,J. (1976). The inhibitory effect of adenosine and related nucleotides on the release of acetylcholine. Neuroscience 1, 391-398.
100. von,K., I and Starke,K. (1991). Noradrenaline-ATP co-transmission in the sympathetic nervous system. Trends Pharmacol.Sci. 12, 319-324.
101. Wang,C.M., Chang,Y.Y., Kuo,J.S., and Sun,S.H. (2002). Activation of P2X(7) receptors induced [(3)H]GABA release from the RBA-2 type-2 astrocyte cell line through a Cl(-)/HCO(3)(-)-dependent mechanism. Glia 37, 8-18.
102. Zambon,A., Bronte,V., Di Virgilio,F., Hanau,S., Steinberg,T.H., Collavo,D., and Zanovello,P. (1994). Role of extracellular ATP in cell-mediated cytotoxicity: a study with ATP-sensitive and ATP-resistant macrophages. Cell Immunol. 156, 458-467.
103. Zhang,H.Y. and Young,A.P. (1991). A single upstream glucocorticoid response element juxtaposed to an AP1/ATF/CRE-like site renders the chicken glutamine synthetase gene hormonally inducible in transfected retina. J.Biol.Chem. 266, 24332-24338.
104. Zheng,L.M., Zychlinsky,A., Liu,C.C., Ojcius,D.M., and Young,J.D. (1991). Extracellular ATP as a trigger for apoptosis or programmed cell death. J.Cell Biol. 112, 279-288.