Abstract
To obtain further evidence that the inhibitory neurotransmitter GABA functions in palate development, the presence of an active GABA uptake mechanism was sought using primary cultures of embryonic palate mesenchymal cells. Uptake was compared from cells of two inbred mouse strains in which the SWV strain shows greater sensitivity than the AJ strain to effects of GABA on palate morphogenesis and of diazepam in producing cleft palate (1). Palate cells were capable of accumulating [3H]GABA by saturable uptake mechanisms characteristic of a high and a low affinity active transport as indicated by temperature, Na+ ion and carrier dependence as well asK m andV max values that were comparable to other biological systems. TheV max of the high-affinity uptake system from cells of the SWV strain was 1.8 fold higher than that of the AJ. GABA uptake was also observed in fibroblasts from various sources including embryonic mouse limb cells, human skin fibroblasts and 3T3 cells When active GABA uptake was measured in skin fibroblasts from the mouse SWV and AJ strains, the rate of uptake from SWV cells under high affinity conditions was also 1.8 fold greater than in AJ cells. Thus active GABA uptake appears to be genetically regulated in non-neural cells which may contribute to differential resonses to GABA.
Similar content being viewed by others
References
Wee, E. L., andZimmerman, E. F. 1983. Involvement of GABA in palate morphogenesis and its relation to diazepam teratogenesis in two mouse strains. Teratology 28:15–22.
Krnjevic, K. 1979. Adv. Exp. Med. Biol. 123, Pages 271–286,in Mandel, P., andDefeudis, F. V. (eds.), GABA-Biochemistry and CNS Functions, Plenum Press, New York.
Balcar, V. J., Mark, J., Borg, J., andMandel, P. 1979. High-affinity uptake of γ-aminobutyric acid in cultured glial and neuronal cells. Neurochem. Res. 4:339–354.
Schousboe, A., Hertz, L., andSvenneby, G. 1977. Uptake and metabolism of GABA in astrocytes cultured from dissociated mouse brain hemispheres Neurochem. Res. 2:217–229.
Okada, Y., Taniguchi, H., andShimada, C. 1976. High concentration of GABA and high glutamate decarboxylase activity in rat pancreatic islets and human insulinoma. Science 194:620–622.
Del Rio, R. M., andCaballero, A. L. 1980. Presence of γ-aminobutyric acid in rat ovary. J. Neurochem. 34:1584–1586.
Erdö, S. L., Rosdy, B., andSzporny., L. 1982. Higher GABA concentrations in fallopian tube than in brain of the rat. J. Neurochem. 38:1174–1176.
Kelly, J. S., andDick, F. 1975. Differential labeling, of glial cells and GABA-inhibitory interneurons and nerve terminals following the microinjection of [3H]β-alanine, [3H]DABA and [3H]GABA into single folia of the cerebellum. Cold Spring Harbor Symp. Quant. Biol. 9:93–106.
Erdö, S. L. 1983. High-affinity, sodium-dependent γ-aminobutyric acid uptake by slices of rat ovary. J. Neurochem. 40:582–584.
Enns, L., andMcCoy, E. E. 1980. A study of γ-aminobutyric acid uptake in normal and Down's syndrome platelets. Br. J. Pharmacol. 71:553–556.
Lawrence, I. E. Jr., andBurden, H. W. 1973. Catecholamines and morphogenesis of the chick neural tube and notochord. Am. J. Anat. 137:199–208.
Wallace, J. A. 1982. Monoamines in the early chick embryo: Demonstration of serotonin synthesis and the regional distribution of serotonin.-concentrating cells during morphogenesis. Am. J. Anat. 165:261–276.
Gustafson, T., andToneby, M. 1970. On the role of serotonin and acetylcholine in sea urchin morphogenesis. Exp. Cell Res. 62:102–117.
Buznikov, G. A., andShmukler, Y. B. 1981. Possible role of “prenervous” neurotransmitters in cellular interactions of early embryogenesis: A hypothesis. Neurochem. Res. 6:55–68.
Toneby, M. 1977. Functional aspects of 5-hydroxytryptamine and dopamine in early embryogenesis of Echinodea and Astersidea. University of Stockholm, Stockholm Sweden.
Palén, K., Thorneby, L., andEmanuelsson, H. 1979. Effects of serotonin and serotonin antagonists on chick embryogenesis. Wilhelm Roux' Archives 187:89–103.
Zimmerman, E. F., andWee, E. L. 1984. Role of neurotransmitters in palate development. Pages 37–63.in Zimmerman, E. F. (vol. ed.), Palate Development: Normal and Abnormal Cellular and Molecular Aspects. Current Topics in Developmental Biology. Vol. 19. Academic Press, New York.
Wee, E. L., Babiarz, B. S., Zimmerman, S., andZimmerman, E. F. 1979. Palate morphogenesis: IV. Effects of serotonin and its antagonists on rotation in embryo culture. J. Embryol. Exp. Morph. 53:75–90.
Wee, E. L., Phillips, N. J., Babiarz, B. S., andZimmerman, E. F. 1980. Palate morphogenesis: V. Effects of cholinergic agonists, and antagonists on rotation in embryo culture. J. Embryol. Exp. Morph. 58:177–193.
Snyder, S. H. 1984. Drug and neurotransmitters in the brain. Science 224:22–31.
Miller, R. P., andBecker, B. A. 1975. Teratogenicity of oral diazepam and diphenylhydantoin in mice. Toxicol. Appl. Pharmacol. 32:53–61.
Norman, E. J., Wee, E. L., Berry, H. K. andZimmerman, E. F. 1985. Rapid gas chromatography mass spectrometry quantitation of gamma-aminobutyric acid in biological specimens. J. Chromatog. 337:21–27.
Wee, E. L., Kujawa, M., andZimmerman, E. F. 1981. Palate morphogenesis: VI. Identification of stellate cells in culture. Cell. Tissue Res. 217:143–154.
Bradford, M. M. 1976. A rapid and sensitive method for the quantiation of microgram quantitites of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72:248–254.
Farb, D. H., Berg, D. K., andFishbach, G. D. 1979. Uptake and release of [3H]γ-aminobutyric acid by embryonic spinal cord neurons in dissociated cell culture. J. Cell Biol. 80:651–661.
Iversen, L. L., andJohnston, G. A. R. 1971. GABA uptake in rat central nervous system: Comparison of uptake in slices and homogenates and the effects of some inhibitors. J. Neurochem. 18:1939–1950.
Iversen, L. L., andNeal, M. J. 1968. The uptake of [3H]GABA by slices of rat cerebral cortex. J. Neurochem. 15:1141–1149.
Yu, A. C. H., andHertz, L. 1982. Uptake of glutamate, GABA, and glutamine into a predominately GABA-ergic and a predominantly glutaminergic nerve cell population in culture. J. Neurosci. Res. 7:23–35.
Taniguchi, H., Okada, Y., Hosaya, Y., andBaba, S. 1980. Comparison of uptake of γ-aminobutyric acid by pancreatic islets and by substantia nigra. Biomed. Res. (Suppl.) 1:175–179.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wee, E.L., Zimmerman, E.F. GABA uptake in embryonic palate mesenchymal cells of two mouse strains. Neurochem Res 10, 1673–1688 (1985). https://doi.org/10.1007/BF00988609
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00988609