Summary
The mercurials, p-hydroxymercuribenzoate and p-chloromercuriphenylsulphonate, administered electrophoretically from multi-barelled micropipettes, potentiate the depressant action of similarly administered glycine on feline spinal neurones. In addition, these mercurials inhibit the transport of glycine into rat brain slices. Neither action is very specific for glycine, since slightly higher concentrations of p-chloromercuriphenylsulphonate than those required to potentiate glycine-induced depression also potentiate depression induced by GABA, β-alanine, Land D-α-alanine, and even higher concentrations enhance the excitant action of acidic amino acids. p-Hydroxymercuribenzoate also inhibits the uptake of GABA, DL-aspartate and L-lysine by brain slices. The potentiation by the mercurials of amino acid-induced effects is considered likely to be the result of inhibition of transport processes rather than enzymic activities.
Thiosemicarbazide, administered electrophoretically and intravenously, does not enhance the effects of amino acid excitants or depressants on spinal interneurones. Hydrazinopropionic acid, a potent inhibitor of GABA transaminase, does not enhance GABA-induced depression of spinal interneurones when administered electrophoretically.
These findings suggest the importance of transport processes in the removal of amino acids from the synaptic environment, and evidence is discussed that these processes are likely to differ in detail from the observed gross transport of amino acids into tissue slices.
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References
Alberioi, M., Rodriguez de Lores Arnaiz, G., De Robertis, E.: Glutamic acid decarboxylase inhibition and ultrastractural changes by the convulsant drug allylglycine. Biochem. Pharmacol. 18, 137–143 (1969).
Battistin, L., Grynbaum, A., Lajtha, A.: Distribution and uptake of amino acids in various regions of the cat brain in vitro. J. Neurochem. 16, 1459–1468 (1969).
Baxter, C.F., Roberts, E.: The γ-aminobutyric acid-α-ketoglutaric acid transaminase of beef brain. J. biol. Chem. 233, 1135–1139 (1958).
Blasberg, R., Lajtha, A.: Heterogeneity of the mediated transport system of amino acid uptake in brain. Brain Res. 1, 86–104 (1966).
Carmi, A., Pollack, G., Yellin, H.: α-Hydrazino-acids. I. α-Hydrazino aliphatic acids and α-(1-methylhydrazino) aliphatic acids. J.org.Chem. 25, 44–46 (1960).
Crawford, J.M., Curtis, D.R.: The excitation and depression of mammalian cortical neurones by amino acids. Brit. J. Pharmacol. 23, 313–329 (1964).
Curtis, D.R.: Microelectrophoresis. In: Physical Techniques in Biological Research, Vol. 5, pp. 144–190. Ed. by W.L. Nastuk. New York: Academic Press 1964.
—: The pharmacology of spinal postsynaptic inhibition. Prog. Brain Res. 31, 171–189 (1969).
- Amino acid transmitters in the mammalian central nervous system. Proc. IV Internat. Congress for Pharmacol. (Basel) (in press) (1970).
—, Hösli, L., Johnston, G.A.R.: A pharmacological study of the depression of spinal neurones by glycine and related amino acids. Exp. Brain Res. 6, 1–18 (1968a).
—, Johnston, I.H.: The hyperpolarization of spinal motoneurones by glycine and related amino acids. Exp. Brain Res. 5, 235–258 (1968b).
—, Johnston, G.A.R.: Amino acid transmitters. In: Handbook of Neurochemistry, Vol. 4, pp. 115–135. Ed. by A. Lajtha. New York: Plenum Press 1970.
—, Phillis, J.W., Watkins, J.C.: The chemical excitation of spinal neurones by certain acidic amino acids. J. Physiol. (Lond.) 150, 656–682 (1960).
—, Ryall, R.W.: The acetylcholine receptors of Renshaw cells. Exp. Brain Res. 2, 66–80 (1966).
—, Watkins, J.C.: The excitation and depression of spinal neurones by structurally related amino acids. J. Neurochem. 6, 117–141 (1960).
—: Acidic amino acids with strong excitatory actions on mammalian neurones. J. Physiol. (Lond.) 166, 1–14 (1963).
—: The pharmacology of amino acids related to gamma-aminobutyric acid. Pharmacol. Rev. 17, 347–392 (1965).
De Marchi, W.J., Johnston, G.A.R.: The oxidation of glycine by D-amino acid oxidase in extracts of mammalian central nervous tissue. J. Neurochem. 16, 355–361 (1968).
Giacobini, E.: The effect of metabolic and ion transport inhibitors on the impulse activity and oxygen uptake of an isolated crustacean neurone. Acta physiol. scand. 66, 34–48 (1966).
Graham, L.T., Aprison, M.H.: Distribution of some enzymes associated with the metabolism of glutamate, aspartate, γ-aminobutyrate and glutamine in cat spinal cord. J. Neurochem. 16, 559–566 (1969).
Iversen, L.L., Kravitz, E.A.: The metabolism of γ-aminobutyric acid (GABA) in the lobster nervous system uptake of GABA in nerve-muscle preparations. J. Neurochem. 15, 609 to 620 (1968).
—, Neal, M.J.: The uptake — of [3H] GABA by slices of rat cerebral cortex. J. Neurochem. 15, 1141–1149 (1968).
—, Snyder, S.H.: Synaptosomes: different populations storing catecholamines and gamma aminobutyric acid in homogenates of rat brain. Nature (Lond.) 220, 796–798 (1968).
Jaeger, J.C.: Diffusion from constrictions. In: Studies in physiology, presented to John C. Eccles, pp. 106–117. Ed. by D.R. Curtis and A.K. McIntyre. Berlin-Heidelberg-New York: Springer 1965.
Johnston, G.A.R., Vitali, M.V.: Glycine-producing transaminase activity in extracts of spinal cord. Brain Res. 12, 471–472 (1969a).
—: Glycine: 2-oxoglutarate transaminase in rat cerebral cortex. Brain Res. 15, 201–208 (1969b).
Karlin, A., Bartels, E.: Effects of blocking sulfhydryl groups and of reducing disulfide bonds on the acetylcholine-activated permeability system of the electroplax. Biochem. biophys. Acta (Amst.) 126, 525–535 (1966).
Kleinzeller, A., Cort, J.H.: The mechanism of action of mercurial preparations on transport processes and the role of thiol groups in the cell membrane of renal tubular cells. Biochem. J. 67, 15–24 (1957).
Kuhar, M.J., Snyder, S.H.: The subcellular localization of free H3-glutamic acid in rat cerebral cortical slices. J. Pharmacol. exp. Ther. 171, 141–152 (1970).
Le Fevre, P.G.: Evidence of active transfer of certain non-electrolytes across the human red cell membrane. J. gen. Physiol. 31, 505–527 (1948).
Levi, G., Kandera, J., Lajtha, A.: Control of cerebral metabolite levels. I. Amino acid uptake and levels in various species. Arch. Biochem. Biophys. 119, 303–311 (1967).
—, Lajtha, A.: Cerebral amino acid transport in vitro. II. Regional differences in amino acid uptake by slices from the central nervous system of the rat. J. Neurochem. 12, 639–648 (1965).
McFarland, D., Wainer, A.: Convulsant properties of allylglycine. Life Sci. (Oxford) 4, 1587–1590 (1965).
Mounter, L.A., Whittaker, V.P.: The effect of thiol and other group-specific reagents on erythrocyte and plasma cholinesterases. Biochem. J. 53, 167–173 (1953).
Navon, S., Lajtha, A.: The uptake of amino acids by particulate fractions from brain. Biochim. biophys. Acta (Amst.) 173, 513–531 (1969).
Neal, M.J., Pickles, H.G.: Uptake of 14C glycine by spinal cord. Nature (Lond.) 222, 679–680 (1969).
Reiser, S., Christiansen, P.A.: Intestinal transport of amino acids studied with L-valine. Amer. J. Physiol. 208, 914–921 (1965).
Roberts, E., Kuriyama, K.: Biochemical-physiological correlations in studies of the γ-amino butyric acid system. Brain Res. 8, 1–35 (1968).
—, Simonsen, D.G.: Some properties of L-glutamic decarboxylase in mouse brain. Biochem. Pharmacol. 12, 113–134 (1963).
Sano, K., Roberts, E.: Binding of γ-aminobutyric acid by mouse brain preparations. Biochem. Pharmacol. 12, 489–502 (1963).
Schneider, J.H., Cassir, R., Chrodikian, F.: Inhibition of incorporation of thymidine into deoxyribonucleic acid by amino acid antagonists in vivo. J. biol. Chem. 235, 1437–1440 (1960).
Steiner, F.A., Ruf, K.: Excitatory effects of L-glutamic acid upon single unit activity in rat brain and their modification by thiosemicarbazide and pyridoxal-5′-phospate. Helv. Physiol. pharmacol. Acta 24, 181–192 (1966).
—, Ruf, K.: Interactions of L-glutamic acid, gamma-aminobutyric acid and pyridoxal-5′-phosphate at the neuronal level. Schweiz. Arch. Neurol. Psychiat. 100, 310–320 (1967).
Turpajev, T.M., Nistratova, S.N., Putintseva, T.G.: Protein nature of acetylcholine receptor and the role of energy-rich compounds in the realization of acetylcholine action. In: Proc. 1st Internat. Pharmac. Meeting. Vol. 7, pp. 145–155. Ed. by B. Uvnäs. Oxford: Pergamon Press 1961.
Van Gelder, N.M.: Hydrazinopropionic acid: a new inhibitor of aminobutyrate transaminase and glutamate decarboxylase. J. Neurochem. 15, 747–757 (1968).
—: The action in vivo of a structural analogue of GABA: hydrazinopropionic acid. J. Neurochem. 16, 1355–1360 (1969).
Vansteveninck, J., Weed, R.I., Rothstein, A.: Localization of erythrocyte membrane sulphydryl groups essential for glucose transport. J. gen. Physiol. 48, 617–632 (1965).
Velick, S.Z.: Coenzyme binding and the thiol groups of glyceraldehyde-3-phosphate dehydrogenase. J. biol. Chem. 203, 563–573 (1953).
Webb, J.L.: Mercurials. In: Enzyme and Metabolic Inhibitors, Vol. II, pp. 729–986. New York: Academic Press 1966.
Werman, R., Davidoff, R.A., Aprison, M.H.: Inhibitory action of glycine on spinal neurons in the cat. J. Neurophysiol. 31, 81–95 (1968).
Williams, H.L., Bain, J.A.: Convulsive effect of hydrazides: relationship to pyridoxine. Internat. Rev. Neurobiol. 3, 319–348 (1961).
Wilson, V.J., Talbot, W.H.: Integration at an inhibitory interneurone: inhibition of Renshaw cells. Nature (Lond.) 200, 1325–1327 (1963).
—, Kato, M.: Inhibitory convergence upon Renshaw cells. J. Neurophysiol. 27, 1063 to1079 (1964).
Župančič, A.O.: On the chemical distinctions between cholinesterase and cholinoreceptor. Life Sci. (Oxford) 8, 989–992 (1969).
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Curtis, D.R., Duggan, A.W. & Johnston, G.A.R. The inactivation of extracellularly administered amino acids in the feline spinal cord. Exp Brain Res 10, 447–462 (1970). https://doi.org/10.1007/BF00234262
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DOI: https://doi.org/10.1007/BF00234262