Release of ATP from cultured rat astrocytes elicited by glutamate receptor activation

• Published in: Neuroscience Vol. 78; no. 4; pp. 1203 - 1208
• Main Authors: Queiroz, G, Gebicke-Haerter, P.J, Schobert, A, Starke, K, von Kügelgen, I
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-06-1997; Elsevier
• Subjects: Adenosine Triphosphate - metabolism; AMPA receptor; Animals; Animals, Newborn; Astrocytes - metabolism; ATP release; Biological and medical sciences; Cells, Cultured; Excitatory Amino Acid Agonists - pharmacology; Excitatory Amino Acid Antagonists - pharmacology; Fundamental and applied biological sciences. Psychology; Isolated neuron and nerve. Neuroglia; kainate receptor; L-Lactate Dehydrogenase - metabolism; lactate dehydrogenase release; NMDA receptor; rat astrocytes; Rats; Rats, Wistar; Receptors, Glutamate - physiology; Vertebrates: nervous system and sense organs; NBQX, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline; kainate receptor; AMPA, α-amino-3-hydroxy-5-methylisoxazole-4-propionate; LDH, lactate dehydrogenase; NADH, reduced nicotinamide adenine dinucleotide; lactate dehydrogenase release; AP5, 2-amino-5-phosphonopentanoate; AMPA receptor; ATP release; GAMS, d-glutamyl-amino-methanesulfonate; rat astrocytes; NMDA receptor; NMDA, N-methyl- d-aspartate; Rat; Neuroglia; Rodentia; Central nervous system; Glutamate receptor; Astrocyte; In vitro; Vertebrata; Mammalia; Neurotransmitter; Excitatory aminoacid; ATP; Release; Brain (vertebrata)
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/S0306-4522(96)00637-9

The release of ATP was studied in cultures of astrocytes derived from the brain hemispheres of newborn rats. There was a basal efflux of ATP, which was increased up to 19-fold by glutamate (300–1000
μM),
N-methyl-
d-aspartate (20–500
μM),
α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA; 30–100
μM) and kainate (20
μM). The
N-methyl-
d-aspartate receptor-selective antagonist 2-amino-5-phosphonopentanoate (100
μM) blocked the effect of
N-methyl-
d-aspartate but not the effects of AMPA, kainate and glutamate. The AMPA receptor-selective antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (30
μM) blocked the effect of AMPA and also of glutamate and
N-methyl-
d-aspartate, but not the effect of kainate. The kainate receptor-selective antagonist
d-glutamyl-amino-methanesulfonate (30
μM) blocked the effect of kainate but not of glutamate. Glutamate (1000
μM) did not increase the release of lactate dehydrogenase from astrocytes.
Excitatory amino acids are known to release adenyl compounds in the brain. The present results identify one adenyl compound thus released, namely ATP, and identify astrocytes as one source. The release is brought about by activation of any of the three ionotropic glutamate receptor types—
N-methyl-
d-aspartate, AMPA and kainate receptors. AMPA receptors seem to mediate at least a part of the effect of glutamate itself, but the involvement of other receptors cannot be ruled out. ATP and its degradation products, such as adenosine, once released, may exert acute as well as trophic effects on neurons and glial cells.