Summary
The present study describes a simplified on-line system for determination of GABA in brain dialysates. GABA was determined with an isocratic HPLC method after derivatization with o-phtaldialdehyde. One peristaltic pump was sufficient to transport both the perfusion fluid and the derivatizing reagent.
The basal release of GABA was stimulated by infusion with either elevated K+ or the GABA uptake inhibitor (−)-nipecotic acid. Basal as well as stimulated GABA release were investigated for possible calcium-dependency by infusing submmolar amounts of the potent calcium antagonist cadmium. Infusion of cadmium did not modify the dialysate concentrations of GABA. In addition basal as well as nipecotic acid enhanced release of GABA dialysate concentrations were investigated for nerve-impulse dependency by infusing μmolar amounts of tetrodotoxin. No change in the GABA output was observed during infusion of TTX. From these results it is concluded that the basal as well as the nipecotic acid induced release of GABA did not fulfill the criteria for classic exocytotic release. Possible explanations for these unexpected findings are discussed.
Similar content being viewed by others
References
Bell JA, Anderson EG (1974) Dissociation between amonooxyacetic acid-induced depression of spinal reflexes and the rise in cord GABA levels. Neuropharmacology 13:885–894
Damsma G, Westerink BHC, Imperato A, Rollema H, De Vries JB, Horn AS (1987) Automated brain dialysis of acetylcholine in freely moving rats: detection of basal acetylcholine. Life Sci 41:873–876
Dietl H, Philippu A (1979) In vivo release of endogenous GABA in the cat hypothalamus. Naunyn-Schmiedeberg's Arch Pharmacol 308:143–147
Girault JA, Barbeito L, Spampinato U, Gozlan H, Glowinski J, Besson MJ (1986a) In vivo release of endogenous amino acids from the rat striatum: further evidence for a role of glutamate and aspartate in corticostriatal neurotransmission. J Neurochem 47:98–106
Girault JA, Spampinato U, Savaki HE, Glowinski J, Besson MJ (1986b) In vivo release of [3H]γ-aminobutyric acid in the rat neostriatum. I. Characterization and topographical heterogeneity of the effects of dopaminergic and cholinergic agents. Neuroscience 19:1101–1108
Hamberger A, Berthold C-H, Karlsson B, Lehmann A, Nyström B (1983) Extracellular GABA, glutamate and glutamine in vivo perfusion-dialysis of the rabbit hippocampus. In: Hertz L, Kvamme E, McGeer EG, Shousbou A (eds) Glutamine, glutamate, and GABA in the central nervous system. Alan Riss, New York, pp 473–492
Henn FA, Hamberger A (1971) Glial cell function: uptake of transmitter substances. Proc Natl Acad Sci USA 68:2686–2690
Floran B, Silva I, Nana C, Aceves J (1988) Presynaptic modulation of the release of GABA by GABA-A receptors in pars compacta and by GABA-B receptors in pars reticulata of the rat substantia nigra. Eur J Pharmacol 150:277–286
I'Heureux R, Dennis T, Curet O, Scatton B (1986) Measurement of endogenous noradrenaline release in the rat cerebral cortex in vivo by transcortical dialysis: effects of drugs affecting noradrenergic transmission. J Neurochem 46:1794–1801
Imperato A, Di Chiara G (1984) Trans-striatal dialysis coupled to reverse phase high performance liquid chromatography with electrochemical detection: a new method for the study of the in vivo release of endogenous dopamine and metabolites. J Neurosci 4:966–977
Jaffe EH, Hernandez N, Holder L (1984) Study of the mechanisms of release of [3H]GABA from a teleost retina in vitro. J Neurochem 43:1226–1233
Katz B (1969) The release of neural transmitter substances. Liverpool University Press, Liverpool
Kalén P, Strecker RE, Rosengren E, Björklund A (1988) Endogenous release of neuronal serotonin and 5-HIAA in the caudateputamen of the rat as revealed by intracerebral dialysis coupled to high performance liquid chromatography with fluorimetric detection. J Neurochem (in press)
Kehr J, Ungerstedt U (1988) Fast HPLC estimation of γ-amino-butyric acid in microdialysis perfusates: effect of nipecotic and 3-mercaptopropionic acids. J Neurochem 51:1308–1310
König JFR, Klippel RA (1963) The rat brain. A stereotaxic atlas of the forebrain and lower parts of the brain stem. Williams and Wilkins, Baltimore
Miller RJ (1987) Multiple calcium channels and neuronal function. Science 235:46–52
Minchin MCW, Iversen LL (1974) Release of 3H-GABA from glial cells in rat dorsal root ganglia. J Neurochem 23:533–540
Neal ML, Bowery NG (1979) Differential effects of veratridine and potassium depolarization on neuronal and glial GABA release. Brain Res 167:337–343
Potashner SJ (1978) Effects of tetrodotoxin, calcium and magnesium on the release of amino acids from slices of guinea-pig cerebral cortex. J Neurochem 31:187–195
Sellström A, Hamberger A (1977) Potassium-stimulated gammaaminobutyric acid release from neurons and glia. Brain Res 119:189–198
Tossman U, Jonsson G, Ungerstedt U (1986) Regional distribution and extracellular levels of amino acids in rat central nervous system. Acta Physiol Scand 127:533–545
Tuomisto L, Yamatodani A, Dietl H, Waldmann U, Phillipu A (1983) In vivo release of endogenous catecholamines, histamine and GABA in the hypothalamus of Wistar Kyoto and spontaneous hypertensive rats. Naunyn-Schmiedeberg's Arch Pharmacol 323:183–187
Van den Berg CJ, Matheson CJ, Nijenmanting WC (1978) Compartmentation of amino acids in the brain: The GABA glutamine-glutamate cycle. In: Fonnum F (ed) Amino acids as chemical transmitters. Plenum Press, New York, pp 709–723
Van der Heyden JAM, Venema K, Korf J (1980) In vivo release of endogenous γ-aminobutyric acid from rat striatum: effects of muscimol, oxotremorine, and morphine. J Neurochem 34: 1648–1653
Waldmeier PC, Wicki P, Feldtrauer J-J, Baumann PA (1988) The measurement of the release of endogenous GABA from rat brain slices by liquid chromatography with electrochemical detection. Naunyn-Schmiedeberg's Arch Pharmacol 337:284–288
Westerink BHC, Tuntler J, Damsma G, Rollema H, De Vries JB (1987a) The use of tetrodotoxin for the characterization of drug-enhanced dopamine release in conscious rats studied by brain dialysis. Naunyn-Schmiedeberg's Arch Pharmacol 336: 502–507
Westerink BHC, Damsma G, Rollema H, De Vries JB, Horn AS (1987b) Scope and limitations of in vivo brain dialysis: a comparison of its application to various neurotransmitter systems. Life Sci 41:1763–1776
Westerink BHC, De Vries JB (1988) Characterization of in vivo dopamine release as determined by brain dialysis after acute and subchronic implantations: methodological aspects. J Neurochem 51:683–687
Westerink BHC, Hofsteede RM, Tuntler J, De Vries JB (1989) The use of calcium antagonism for the characterization of drug-evoked dopamine release from the brain of conscious rats determined by microdialysis. J Neurochem 52:722–729
Yazulla S (1983) Stimulation of GABA release from retinal horizontal cells by potassium and acidic amino acid agonists. Brain Res 275:61–74
Author information
Authors and Affiliations
Additional information
Send offprint requests to B. H. C. Westerink at the above address
Rights and permissions
About this article
Cite this article
Westerink, B.H.C., de Vries, J.B. On the origin of extracellular GABA collected by brain microdialysis and assayed by a simplified on-line method. Naunyn-Schmiedeberg's Arch Pharmacol 339, 603–607 (1989). https://doi.org/10.1007/BF00168650
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00168650