Abstract
P2-fractions were isolated from rat brain, and used to study net taurine transport. The fractions were incubated in increasing concentrations of [3H]taurine and the intraterminal concentration measured by liquid scintillation and amino acid analysis. The membrane potential of the isolated fractions was estimated using86Rb+ as a marker for intracellular K+. Taurine was synthesized in the P2-fraction when incubated in taurine free medium. At external taurine concentrations below 370 μM a significant amount of the endogenous taurine was released to the incubation medium. Net taurine uptake into the P2-fraction was achieved at external taurine concentrations exceeding 370 μM. The taurine antagonist 6-aminomethyl-3-methyl-4H, 1, 2, 4-benzothiadiazine-1, 1-dioxide (TAG) competitively inhibited taurine and [3H]taurine transport into the P2-fraction. As the external concentration of taurine was increased, the accumulation of86Rb+ into the P2-fraction was facilitated. This indicated an increasing hyperpolarization of the neuronal membrane as taurine transport shifted from release towards uptake. TAG reduced the hyperpolarization that paralleled taurine accumulation, in a dose dependent manner. Our results indicate that relatively low transmembranal gradients of taurine may be maintained by an electrogenic taurine transporter having a large transport capacity. Such a transporter may well serve the needs of osmotic regulation, i.e. to transport large amounts of taurine in any direction across the neuronal membrane.
Similar content being viewed by others
References
Huxtable, R. J. 1989. Taurine in the central nervous system and the mammalian actions of taurine. Prog. Neurobiol. 32:471–533.
Saransaari, P., and Oja, S. S. 1992. Release of GABA and taurine from brain slices. Prog. Neurobiol. 38:455–482.
Shain, W., and Martin, D. L. 1990. Uptake and release of taurine—an overview. In Taurine: Functional Neurochemistry, Physiology, and Cardiology, Eds. Pasantes.Morales, H. et al., Wiley-Liss, NY, 243–252.
Trachtman, H., Futterweit, S., and del Pizzo, R. 1992. Taurine and osmoregulation. IV. Cerebral taurine transport is increased in rats with hypernatremic dehydration. Pediatr. Res. 32:118–124.
Sánchez-Olea, R., Morán, J., and Pasantes-Morales, H. 1992. Changes in taurine transport evoked by hyperosmolarity in cultured astrocytes. J. Neurosci. Res. 32:86–92.
Liu, Q.-R., López-Corcuera, B., Nelson, H., Mandiyan, S., and Nelson, N. 1992. Cloning and expression of a cDNA encoding the transporter of taurine and β-alanine in mouse brain. Proc. Natl. Acad. Sci. 89:12145–12149.
Smith, K. E., Borden, L. A., Wang, S.-H. D. Harting, P. R., Branchek, T. A., and Weinshank, R. L. 1992. Cloning and expression of a high affinity taurine transporter from rat brain. Mol. Pharmacol. 42:563–569.
Uchida, S., Kwon, H. M., Yamauchi, A., Preston, A. S., Marumo, F., and Handler, J. S. 1992. Molecular cloning of the cDNA for an MDCK cell Na+- and Cl−-dependent taurine transporter that is regulated by hypertonicity. Proc. Natl. Acad. Sci. 89:8230–8234.
Rassin, D. K. 1982. Taurine, cysteine sulfinic acid decarboxylase and glutamine acid in brain. Pages 259–268,in R. J. Hu and H. Pasantes-Morales (eds), Taurine in nutrition and neurology. Plenum., New York.
Almarghini, K., Remy, A., and Tappaz, M. 1991. Immunocytochemistry of the taurine biosynthesis enzyme, cysteine sulfinate decarboxylase, in the cerebellum: evidence for a glial localization. Neuroscience 43:111–119.
Oja, S. S., Kontro, P., and Lähdesmäki, P. 1977. Amino acids as inhibitory neurotransmitters. Prog. Pharmacol. 1(3):1–119.
Oja, S. S., and Korpi, E. R. 1983. Amino acid transport. Pages 311–337in A. Lajtha (Ed), Handbook of Neurochemistry, Vol. 5, 2nd ed. Plenum, New York.
Lidén, E., Karlsson, L., and Sellström, Å. 1986. Is the concentration of γ-aminobutyric acid in the nerve terminal regulated via product inhibition of glutamic acid decarboxylase? Neurochem. Res. 12:489–493.
Sellström, Å., Venema, R., and Henn, F. A. 1976. Functional assessment of GABA uptake or exchange by synaptosomal fractions. Nature 264:652–653.
Halvarsson, G. B., Barlsson, I., and Sellström, Å. 1985. The use of3H-γ-aminobutyric acid for transport studies with isolated nerveterminals from rat brain. Life Sci. 37:209–216.
Debler, E. A., and Lajtha, A. 1987. High-affinity transport of γ-aminobutyric acid, glycine, taurine, L-aspartic acid and L-glutamic acid in synaptosomal (P2) tissue: A kinetic and substrate specificity analysis. J. Neurochem. 48:1851–1856.
Benveniste, H., Dejer, J., Schousboe, A., and Diemer, N. H. 1984. Elevation of the extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis. J. Neurochem. 43:1369–1374.
Jacobson, I., and Hamberger, A. 1984. Veratridine-induced release in vivo and in vitro of amino acids in the rabbit olfactory bulb. Brain Res. 299:103–112.
Butcher, S. P., and Hamberger, A. 1987. In vivo studies on the extracellular, and veratridine-releasable, pools of endogenous amino acids in the rat striatum: Effects of corticostriatal deafferentation and kainic acid lesion. J. Neurochem. 48:713–721.
Kumar, M. J., and Zarbin, M. A. 1978. Synaptosomal transport: A chloride dependence for choline, GABA, glycine and several other compounds. J. Neurochem. 31:251–256.
Martin, G. E., Bendesky, R. J., and Williams, M. 1981. Further evidence for selective antagonism of taurine by 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadizaine-1,1-dioxide. Brain Res. 299:530–535.
Yarbrough, G. G., Singh, D. K., and Taylor, D. A. 1981. Neuropharmacological characterization of a taurine antagonist. J. Pharmacol. Exp. Ther. 219:604–613.
Thurston, J. H., Mauhart, R. E., and Dirgo, J. A. 1980. Taurine: a role in osmotic regulation of mammalian brain and possible clinical significance. Life Sci. 26:1561–1568.
Van Gelder, N. M. 1983. A central mechanism of action for taurine: osmoregulation, bivalent cations and excitation threshold. Neurochem. Res. 8:687–699.
Lehman, A., Hagberg, H., and Hamberger, A. 1984. A role for taurine in the maintenance of homeostasis in the central nervous system during hyperexcitation. Neurosci. Lett. 52:341–346.
Pasantes Morales, H., and Schousboe, A. 1988. Volume regulation in astrocytes: A role for taurine as an osmoeffector. J. Neurosci. Res. 20:505–509.
Solis, J. M., Herranz, A. S., Herreras, O., Lerma, J., and Martin del Rio, R. 1988. Does taurine act as an osmoregulatory substance in the rat brain? Neuroscience 91:53–58.
Wade, J. V., Olson, J. P., Samson, F. E., Nelson, S. R., and Pazdernik, T. L. 1988. A possible role for taurine in osmoregulation within the brain. J. Neurochem. 51:740–745.
Martin, D. L., Madelian, V., Seligmann, B., and Shain, W. 1990. The role of osmotic pressure and membrane potential in K+-stimulated taurine release from cultured astrocytes and LRM55 cells, J. Neurosci. 10:571–577.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Lewin, L., Rassin, D.K. & Sellström, Å. Net taurine transport and its inhibition by a taurine antagonist. Neurochem Res 19, 347–352 (1994). https://doi.org/10.1007/BF00971584
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00971584