Summary
The effects of the porphyrin precursor δ-aminolaevulinic acid (ALA) on γ-aminobutyric acid (GABA) and L-glutamate transmitter systems was investigated in rat brain. It was found that ALA inhibited GABA and glutamate uptake and stimulated basal efflux of the amino acids in purified nerve endings. These effects were evident only at relatively high concentrations of ALA (at least 100 μM). Such concentrations probably do not occur in the nervous systems of patients suffering from acute porphyria. In addition, it was found that ALA inhibited the stimulated release of GABA from nerve endings probably by acting as an agonist at GABA autoreceptors. This effect was found at very low concentrations of ALA (1 μM). It is therefore likely that the neuropsychiatric manifestations of the acute porphyric attack are attributable, to some extent, to reduced GABA release at central synapses.
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References
Bloomer, J. R., 1976. Gastroenterology 71: 689–701.
Elder, G. H., Gray, C. H. & Nicholson, D. C., 1972. J. Clin. Pathol. 25: 1013–1033.
Pimstone, N., 1975. Mod. Trends Gastroenterology 5: 375–381.
Tschudy, D. P., Valsamis, M. & Magnussen, C. R., 1975. Ann. Intern. Med. 83: 851–864.
Goldberg, A., 1959. Q. J. Med. 28: 183–209.
Stein, J. A. & Tschudy, D. P., 1970. Medicine 49: 1–16.
Dean, G., 1971. The Porphyrias; A story of inheritance and environment, Pitman, London.
Eales, L., 1963. S. Afr. J. Lab. Clin. Med. 9: 151–162.
Goldberg, A., Rimington, C. & Lockhead, A., 1967. Lancet i: 623–636.
McIntyre, N., Pearson, A. J. G., Allan, D. J., Craske, S., West, G. M. I., Moore, M. R., Beattie, A. D., Paxton, J. & Goldberg, A., 1971. Lancet i: 560–564.
Becker, D. M., 1972. PhD thesis, University of the Witwatersrand, Johannesburg.
Ackner, B., Cooper, J. E., Gray, C. H., Kelley, M. & Nicholson, D. C., 1961. Lancet i: 1256–1260.
Bonkowsky, H. L., Tschudy, D. P., Collins, A., Doherty, J., Bossenmaier, I., Cardinal, R. & Watson, C. J., 1971. Proc. Natl. Acad. Sci. U.S.A. 68: 2725–2729.
Sweeney, V. P., Pathak, M. A. & Asbury, A. K., 1970. Brain 93: 369–380.
McGillion, F. B., Moore, M. R. & Goldberg, A., 1973. Scot. Med. J. 18: 133.
McGillion, F. B., Thompson, G. G., Moore, M. R. & Goldberg, A., 1974. Biochem. Pharmacol. 23: 472–474.
McGillion, F. B., Thompson, G. G. & Goldberg, A., 1975. Biochem. Pharmacol. 24: 299–301.
Becker, D. M., Kramer, S. & Viljoen, J. D., 1974. J. Neurochem. 23: 1019–1023.
Welland, F. H., Hellman, E. S., Gaddis, E. M., Collins, A., Hunter, G. W. & Tschudy, D. P., 1964. Metabolism 13: 232–250.
Bonkowsky, H. L., Magnussen, C. R., Collins, A. R., Doherty, J. M., Hess, R. A. & Tschudy, D. P., 1976. Metabolism 25: 405–414.
Watson, C. J., Dhar, G. J., Bossenmaier, I., Cardinal, R. & Petryka, Z. J., 1973. Ann. Intern. Med. 79: 80–83.
Watson, C. J., 1975. New Engl. J. Med. 293: 605–607.
Dhar, G. J., Bossenmaier, I., Petryka, Z. J., Cardinal, R. & Watson, C. J., 1975. Ann. Intern. Med. 83: 20–30.
Petersen, A., Bossenmaier, I., Cardinal, R. & Watson, C. J., 1976. J. Am. Med. Ass. 235: 520–522.
Watson, C. J., Pierach, C. A., Bossenmaier, I. & Cardinal, R., 1977. Proc. Natl. Acad. Sci. U.S.A. 74: 2118–2120.
Blum, I. & Atsmon, A., 1976. S. Afr. Med. J. 50: 898–899.
Goldberg, A., Paton, W. D. M. & Thompson, J. W., 1954. Br. J. Pharmacol. 9: 91–94.
Jarrett, A., Rimington, C. & Willoughby, D. A., 1956. Lancet i: 125–127.
Marcus, R. J., Wetterberg, L. Yuwiler, A. & Winters, W. D., 1970. Electroencephalogr. Clin. Neurophysiol. 29: 602–607.
Shanley, B. C., Taljaard, J. J. F., Deppe, W. M. & Joubert, S. M., 1972. S. Afr. Med. J. 46: 84.
Biempica, L., Kosower, V. & Novikoff, A., 1967. Lab. Invest. 17: 171–189.
Yuwiler, A., Wetterberg, L. & Geller, E., 1970. Biochem. Pharmacol. 19: 189–195.
Kosower, N. & Rock, R. A., 1968. Nature 217: 565–567.
DeMatteis, F. & Rimington, C., 1962. Lancet i: 1332–1334.
Shanley, B. C., Neethling, A. C., Percy, V. A. & Carstens, H., 1975. S. Afr. Med. J. 49: 576–580.
Feldman, D. S., Levere, R. D. & Lieberman, J. S., 1968. J. Clin. Invest. 47: 33A.
Feldman, D. S., Levere, R. D., Lieberman, J. S., Cardinal, R. A. & Watson, C. J., 1971. Proc. Natl. Acad. Sci. U.S.A. 68: 383–386.
Loots, J. M., Becker, D. M., Meyer, B. J., Goldstuck, N. & Kramer, S., 1975. J. Neural Transm. 36: 71–81.
Becker, D. M., Goldstuck, N. & Kramer, S., 1975. S. Afr. Med. J. 49: 1790–1792.
Becker, D. M., Viljoen, J. D. & Kramer, S., 1971. Biochim. Biophys. Acta 225: 26–34.
Strand, L. J., Meyer, U. A., Felsher, B. F., Redeker, A. G. & Marver, H. S., 1972. J. Clin. Invest. 51: 2530–2536.
Sassa, S., Granick, S., Bickers, D. R., Bradlow, H. L. & Kappas, A., 1974. Proc. Natl. Acad. Sci. U.S.A. 71: 732–736.
Magnussen, C. R., Levine, J. B., Doherty, J. M., Cheeseman, J. O. & Tschudy, D. P., 1974. Blood 44: 857–868.
Sassa, S., Solish, G., Levere, R. D. & Kappas, A., 1975. J. Exp. Med. 142: 722–731.
Bonkowsky, H. L., Tschudy, D. P., Weinbach, E. C., Ebert, P. S. & Doherty, J. M., J. Lab. Clin. Med. 85: 93–102.
Bickers, D. R., Keogh, L., Rifkind, A. B., Harber, L. C. & Kappas, A., 1977. J. Invest. Derm. 68: 5–9.
Mustajoki, P. & Seppalainen, A. M., 1975. Br. Med. J. 2: 310–312.
Song, C. S., Bonkowsky, H. L. & Tschudy, D. P., 1974. Clin. Pharmac. Ther. 15: 431–435.
Anderson, K. E., Alvares, A. P., Sassa, S. & Kappas, A., 1976. Clin. Pharmac. Ther. 19: 47–54.
Meyer, U. A., 1976. Progress in liver diseases (Popper, H. and Schaffner, F., eds.), pp. 280–293, Grune & Stratton, New York.
Irvine, D. G. & Wetterberg, L., 1972. Lancet ii: 1201.
Brodie, M. J., Graham, D. J. M., Thompson, G. G., Moore, M. R. & Goldberg, A., 1976. Clin. Sci. Molec. Med. 50: 431–434.
Irvine, D. G., Bayne, W. & Miyashita, H., 1969. Nature 224: 811–813.
Sohler, A., Beck, R. & Noval, J. J., 1970. Nature 228: 1318–1320.
Jacobson, S. J., Rapport, H. & Ellman, G. L., 1975. Biol. Psychiat. 10: 91–93.
Frydman, R. B., Tomaro, M. L., Frydman, B. & Wanschelbaum, A., 1975. FEBS Lett. 51: 206–210.
Meyer, U. A. & Schmid, R., 1974. Brain dysfunction in metabolic disorders (Plum, F., ed.) Res. Publ. Assoc. Nerv. Ment. Dis. 53: 211–223, Raven Press, New York.
Brennan, M. J. W. & Cantrill, R. C., 1978. J. Neurochem. 31: 1339–1341.
Brennan, M. J. W. & Cantrill, R. C., 1979. J. Neurochem. 32: 1781–1786.
Brennan, M. J. W. & Cantrill, R. C., 1979. J. Neurochem. 33: 721–725.
Cantrill, R. C. & Brennan, M. J. W., 1980. Experientia 36: 141–142.
Enna, S. J. & Snyder, S. H., 1975. Brain Res. 100: 81–97.
Iversen, L. L. & Johnston, G. A. R., 1971. J. Neurochem. 18: 1939–1950.
Henn, F. & Hamberger, A., 1971. Proc. Natl. Acad. Sci. U.S.A. 68: 2686–2690.
Martin, D. L., 1973. J. Neurochem. 21: 345–356.
Somoza, E., Pugnaire, M. P., Munoz, L. M., Portal, C. G., Ibanez, A. E. & DeFeudis, F. V., 1977. J. Neurochem. 28: 1197–2000.
Hitzemann, R. J. & Loh, H. H., 1978. J. Neurochem. 30: 471–477.
Brennan, M. J. W. & Cantrill, R. C., 1979. S. Afr. J. Sci. 75: 126–129.
Levi, G. & Raiteri, M., 1973. Life Sci. 12: 81–88.
Balcar, V. J. & Johnston, G. A. R., 1972. J. Neurobiol. 3: 295–301.
Takagaki, G., 1978. J. Neurochem. 30: 47–56.
Snodgrass, S. R., 1978. Nature 273: 392–394.
Mitchell, P. R. & Martin, I. L., 1978. Nature 274: 904–905.
Brennan, M. J. W., Cantrill, R. C. & Epstein, H., 1979. 4th Natl. Congr. S. Afr. Biochem. Soc. 102.
Brennan, M. J. W. & Cantrill, R. C., 1979. Nature 280: 514–515.
Raiteri, M., Federico, R., Coletti, A. & Levi, G., 1975. J. Neurochem. 24: 1243–1250.
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Brennan, M.J.W., Cantrill, R.C. δ-Aminolaevulinic acid and amino acid neurotransmitters. Mol Cell Biochem 38, 49–58 (1981). https://doi.org/10.1007/BF00235687
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DOI: https://doi.org/10.1007/BF00235687