Glutamatergic Signals in Ephedra

SCIENTIFIC CORRESPONDENCE

Our results and conclusion differ from climate system is zero. Although this kynurenic acids are selective antagonists those of Elsner and Tsonis because we would mean that there is no global-warm­ competing with glycine for binding sites on determine the variance of the white-noise ing problem, it is not consistent with the NMDA and non-NMDA glutamate recep­ forcing for the physical and statistical varied palaeoclimatic history of the Earth. tors13. 6-HKYNA, however, had no activity models, together with the autoregressive Michael E. Schlesinger on the hindgut, whether applied alone coefficients for the latter, from the Department of Atmospheric or together with glutamate or quis­ observed surface temperature record after Sciences, qualate, suggesting that 6-substituted removal of the temperature changes con­ University of Illinois, kynurenic acids are not glutamate receptor tributed by increasing greenhouse gases at Urbana-Champaign, antagonists in insect visceral muscle. and anthropogenic sulphate aerosols, that Illinois 61801, USA 7-Methoxykynurenic acid, reported to 14 is, after detrending. Elsner and Tsonis Navin Ramankutty occur in E. alata , is not a glutamate determine the white-noise variance and Climate, People and receptor antagonist in mammalian 13 autoregressive coefficient for their statis­ Environment Program, neurons • tical model from the nondetrended Institute for Environmental Studies, Most Eurasian species of Ephedra, such observed temperature record. Thus, they University of Wisconsin-Madison, as E. distachya and E. fragilis, contain assume that all temperature changes Madison 53706, USA the sympathomimetic drugs ephedrine, observed since the middle of the nine­ pseudoephedrine and pharmacologically 1. Schlesinger, M. E. & Ramankutty, N. Nature 367, 15 teenth century are due to natural varia­ 723-726 (1994). related amines • Ephedrine in the diet is 2 bility, whereas we assume that only the 2. Broom head, D. S. & King,G. P. Physica 20D, 217-236 toxic to the pea weevil • The ephedrine temperature changes other than those (1986). alkaloids and the tannins present in the 3. Fraedrich, K. J. atmos. Sci. 43, 419-432 (1986). forced by greenhouse gases and anthro­ 4. Folland, C. K. eta/. in Climate Change 1992- The stems of most Eurasian species are absent pogenic sulphate aerosols are due to Supplementary Report to the IPCC Scientific Assessment from E. foeminea, E. altissima and (eds Houghton J. T. eta/.) 135-170 (Cambridge Univ. natural variability. Their assumption Press, 1992). E. foliata (see table). As methanoproline, means that, unless the anthropogenic 5. Allen, M. R. & Smith, L. A. Geophys. Res. Lett. 21, too, is restricted to tannin- and ephedrine­ 883-886 (1994). forcing of the climate system has been 6. Schlesinger, M. E. & Ramankutty, N. Geophys. free species, we propose that cyclopropyl zero year after year, the sensitivity of the Res. Lett. (submitted). amino acids act as an alternative form of feeding deterrent. A possible reason why some Ephedra species are tannin-free may be that tannins block N a+- dependent Glutamatergic signals in Ephedra amino-acid transport, compromising the SIR - Plants frequently synthesize toxic amino-acid metabolism and is a neuro­ defensive role of ingested cyclopropyl non-protein amino acids that disrupt transmitter molecule in vertebrates and amino acids. The ephedrine alkaloids amino-acid transport, metabolism and arthropods, ingestion of L-2-( carboxy­ found in many Ephedra species contain­ protein synthesis in leaf- and seed-eating cyclopropyl)glycines might alter herbivore ing tannins are non-polar and do not 1 2 mammals and insects • • Ephedra foeminea behaviour. We tested the membrane need special transporter proteins for Forssk. (Ephedraceae, Gnetales), the activity of three L-CCG isomers on two their absorption. It is remarkable that, joint-fir, widely distributed in the eastern insect tissues in vitro. A Na +-dependent despite the more than 100 papers pub­ Mediterranean and the near Ease, glutamate transporter in the beetle epi­ lished over the past 100 years or so on contains in its fresh stems substantial dermis7 concentrated both cis-isomers, the alkaloid content of Ephedra, the pres­ amounts of the two cis-diastereoisomers whereas L-CCGIII and L-CCGI (the trans- ence of cyclopropyl amino acids and 6 of the L-glutamate analogue L-2-carboxy­ 2S, 3S, 4S-isomer found inBlighia sapida ) 6-hydroxykynurenic acid has previously cyclopropyl) glycine, (2S, 3S, 4R)­ caused a cockroach hindgut preparation8 gone undetected. and (2S, 3R, 4S)-2-(carboxycyclopropyl) to contract. In mammalian neurons, Stanley Caveney glycine (L-CCGIII and L-CCGIV, respec­ L-CCGIII potentiates responsiveness to Department of Zoology, tively)4. These two compounds, which L-glutamate9 and L-CCGIV activates University of Western Ontario, constitute about 1% of the stem dry the N-methyl D-aspartate (NMDA) sub­ London, Ontario, Canada N6A 587 10 weight in this and a related Mediter­ type of the L-glutamate receptor • Alvin Starratt ranean species, E. altissima (see table), The stems of many Ephedra species Pest Management Research Centre, are rare. L-CCGIII has been reported5 in also contain substantial amounts of a Agriculture and Agri-Food Canada, a few North American species ofAesculus quinoline, 6-hydroxykynurenic acid (6- London, Ontario, Canada N5V 4T3 (the buckeyes). The presence ofL-CCGIV HKYNA), known to occur in trace 1. Hunt, S. in Chemistry and Biochemistry of the Amino 11 in plants has not been reported before. amounts in many plants • In Ginkgo Acids (ed. Barrett, G.C.) 55-138 (Chapman and Hall, London, 1985). The stem tissue of E. foeminea also biloba, a primitive tree notably free of 2. Janzen, D.H., Juster, H.B. & Bell, E.A. Phytochemistry, contains cis-3,4-methano-L-proline, a insect pests, however, it may constitute 223-227 (1977). 2 3. Freitag, H. & Maier-Stolte, M. Taxon 38, 545-556 cyclopropane amino acid previously 0.24% of the leaf dry weighe • Similar (1989). 6 reported only inAesculus pa11Jiflora • amounts are seen in Ephedra (see table). 4. Shimamoto, K. eta/. J. org. Chem. 56, 4167-4176 Because L-glutamate is central to In the mammalian brain, substituted (1991). 5. Fowden, L. Anderson., J.W. & Smith, A. Phytochemistry 9, 2349-2357 (1970). CYCLOPROPYL AMINO ACIDS, 6-HYDROXYKYNURENIC ACID AND EPHEDRINE ALKALOIDS, AND 6. Fowden, L. eta/. Phytochemistry B. 437-443 (1969). 7. Mclean, H. & Caveney, S. J. camp. Physiol. B163, PRESENCE OF TANNINS IN THE FRESH STEMS OF SELECTED EPHEDRA SPECIES 297-306 (1993). 8. Starratt, A.N. & Steele, R.W. in Neurohormonal Techniques in Insects (ed. Miller, T.A.) 1-30 (Springer, Species L-CCGIII L-CCGIV Methano- 6-Hydroxy- Ephedrine Pseudo- Tannins New York, 1980). proline kynurenic acid ephedrine 9. Nakamura, Y., Kataoka, K., Ishida, M., & Shinozaki, H. Neuropharmacology 32, 833-837 (1993). E.foeminea ++++ +++ ++ +++ no 10. Kawai, M. !'tal. Eur. J. Pharmac. 211, 195-202 (1992). E. altissima ++++ +++ ++ + no 11. MacNicol, P.K. Biochem. J. 107, 473-479 (1968). E. foliata ++ +++ + no 12. Schennen, A. & Hoelzl, J. Planta Med. 52, 235-236 (1986). yes E. tragi/is ++ ++ ++++ 13. Leeson, P.D. eta/. J. med. Chem. 34, 1243-1252 (1992). E. distachya ++ ++++ yes 14. Nawwar, M.A.M., Barakat, H.H., Buddrus, J. & Linscheid, M. Phytochemistry 24, 878-879 (1985). Amounts of amino acids and alkaloids are expressed as per cent dry tissue weight: (-), not 15. Hegnauer, R. Chemotaxonomie der Pflanzen Vol VII detected; (+), < 0.05 %; (++), 0.05-0.19%; (+++), 0.2-0.5%; (++++), > 0.5%. Ephedraceae, 546-553 (Birkhauser, Basel, 1989). 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