Second-Messenger Systems Coupled to Metabotropic Glutamate Receptors

  • P. Jeffrey Conn
  • Valerie Boss
  • Dorothy S. Chung
Part of the The Receptors book series (REC)


Glutamate and other excitatory amino acids (EAAs) have long been known to increase the levels of various second-messenger systems in different nervous system preparations. However, until recent years, these effects were generally held to be secondary to activation of glutamate-gated cation channels, and subsequent increases in neurotransmitter release or intracellular calcium concentrations. The first direct evidence for the existence of glutamate receptors directly coupled to second-messenger systems via GTP-binding proteins (G-proteins) came in the mid1980s with the discovery of glutamate receptors coupled to activation of phosphoinositide hydrolysis. Since that time, it has become clear that members of the metabotropic glutamate receptor (mGluR) family are coupled, either directly or indirectly, to a variety of second-messenger systems, including activation of phosphoinositide hydrolysis, regulation of adenylyl cyclase, activation of phospholipase D, increased cyclic guanosine mono-phosphate (cGMP) accumulation, and arachidonic acid release.


Glutamate Receptor Adenylyl Cyclase Hippocampal Slice Metabotropic Glutamate Receptor Cerebellar Granule Cell 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adamson, P., Hajimohammadreza, I., Brammer, M. J., Campbell, I. C., and Meldrum, B. S. (1990) Presynaptic glutamate/quisqualate receptors: effects on synaptosomal free calcium concentrations. J. Neurochem. 55, 1850–1854.PubMedCrossRefGoogle Scholar
  2. Alexander, S. P. H., Hill, S. J., and Kendall, D. A. (1990) Excitatory amino acid-induced formation of inositol phosphates in guinea-pig cerebral cortical slices: involvement of ionotropic or metabotropic receptors? J. Neurochem. 55, 1439–1441.PubMedCrossRefGoogle Scholar
  3. Alexander, S. P. H., Curtis, A. R., Hill, S. J., and Kendall, D. A. (1992) Activation of a metabotropic excitatory amino acid receptor potentiates An adenosine receptor-stimulated cyclic AMP accumulation. Neurosci. Leu. 146, 231–233.CrossRefGoogle Scholar
  4. Ambrosini, A. and Meldolesi, J. (1989) Muscarinic and quisqualate receptor-induced phosphoinositide hydrolysis in primary cultures of striatal and hippocampal neurons. Evidence for differential mechanisms of activation. J. Neurochem. 53, 825–833.PubMedCrossRefGoogle Scholar
  5. Aniksztejn, L., Bregestovski, P., and Ben-Ari, Y. (1991) Selective activation of quisqualate metabotropic receptor potentiates NMDA but not AMPA responses. Eur. J. Pharmacol. 205, 327–328.PubMedCrossRefGoogle Scholar
  6. Aniksztejn, L., Otani, S., and Ben-Ari, Y. (1992) Quisqualate metabotropic receptors modulate NMDA currents and facilitate induction of long-term potentiation through protein kinase C. Eur. J. Neurosci. 4, 500–505.PubMedCrossRefGoogle Scholar
  7. Aramon, I. and Nakanishi, S. (1992) Signal transduction and pharmacological characteristics of a metabotropic glutamate receptor, mGluR1, in transfected CHO cells. Neuron 8, 757–765.CrossRefGoogle Scholar
  8. Aronica, E., Condorelli, D. F., Nicoletti, F., Albani, P. D., Amico, C., and Balazs, R. (1993) Metabotropic glutamate receptors in cultured cerebellar granule cells: developmental profile. J. Neurochem. 60, 559–565.PubMedCrossRefGoogle Scholar
  9. Baba, A. (1987) Neurochemical characterization of cysteine sulfinic acid, an excitatory amino acid, in hippocampus. Japan. J. Pharmacol. 43, 1–7.CrossRefGoogle Scholar
  10. Baba, A., Saga, H., and Hashimoto, H. (1993) Inhibitory glutamate response on cyclic AMP formation in cultured astrocytes. Neurosci. Lett. 149, 182–184.PubMedCrossRefGoogle Scholar
  11. Bashir, Z. I., Bortolotto, Z. A., Davies, C. H., Berretta, N., Irving, A. J., Seal, A. J., Henley, J. M., Jane, D. E., Watkins, J. C., and Collingridge, G. L. (1993) Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors. Nature 363, 347–350.PubMedCrossRefGoogle Scholar
  12. Billah, M. M. (1993) Phospholipase D and cell signalling. Curr. Opinion Immunol. 5, 114–123.CrossRefGoogle Scholar
  13. Billah, M. M. and Anthes, J. C. (1990) The regulation and cellular function of phosphatidylcholine hydrolysis. Biochem. J. 269, 281–291.PubMedGoogle Scholar
  14. Birse, E. F., Eaton, S. A., Jane, D. E., St. Jones, P. L., Porter, R. H. P., Pook, P. C., Sunter, D. C., Udvarhelyi, M., Wharton, B., Roberts, P. J., Salt, T. E., and Watkins, J. C. (1993) Phenylglcine derivatives as new pharmacological tools for investigating the role of metabotropic glutamate receptors in the central nervous system. Neuroscience 3, 481–488.CrossRefGoogle Scholar
  15. Blackstone, C. D., Supattapone, S., and Snyder, S. H. (1989) Inositol phospholipid-linked glutamate receptors mediate cerebellar parallel-fiber-purkinje-cell synaptic transmission. Proc. Natl. Acad. Sci. USA 86, 4316–4320.PubMedCrossRefGoogle Scholar
  16. Boss, V. and Conn, P. J. (1992) Metabotropic excitatory amino acid receptor activation stimulates phospholipase D in hippocampal slices. J. Neurochem. 59, 2340–2343.PubMedCrossRefGoogle Scholar
  17. Boss, V., Nutt, K. M., and Conn, P. J. (1993) L-Cysteine sulfinic acid as an endogenous agonist of a novel metabotropic receptor coupled to stimulation of phospholipase D activity. Mol. Pharmacol. (in press).Google Scholar
  18. Boss V., Desai M. A., Smith, T. S., and Conn, P. J. (1992) Trans-ACPD-induced phosphoinositide hydrolysis and modulation of hippocampal pyramidal cell excitability do not undergo parallel developmental regulation. Brain Res. 594, 181–188.PubMedCrossRefGoogle Scholar
  19. Bouchelouche, P., Belhage, B., Frandsen, A., Drejer, J., and Schousboe, A. (1989) Glutamate receptor activation in cultured cerebellar granule cells increases cytosolic free Cat+ and activation of Cat* influx. Exp. Brain Res. 76, 281–291.PubMedCrossRefGoogle Scholar
  20. Bredt, D. S. and Snyder, S. H. (1989) Nitric oxide mediates glutamate-linked enhancement of cGMP levels in the cerebellum. Proc. Natl. Acad. Sci. USA 86, 9030–9033.PubMedCrossRefGoogle Scholar
  21. Briley, P. A., Kouyoumdjian, J. C., Maidamous, M., and Gonnard, P. (1979) Effect of L-glutamate and kainate on rat cerebellar cGMP levels in vivo. Eur. J. Pharmacol. 54, 181–184.PubMedCrossRefGoogle Scholar
  22. Bruns, R. F., Pons, F., and Daly, J. W. (1980) Glutamate-and veratridine-elicited accumulations of cyclic AMP in brain slices: a role for factors which potentiate adenosine-responsive systems. Brain Res. 189, 550–555.PubMedCrossRefGoogle Scholar
  23. Cartmell, J., Kemp, J. A., Alexander, S. P. H., Hill, S. J., and Kendall, D. A. (1992) Inhibition of forskolin-stimulated cyclic AMP formation by 1–aminocyclopentane-trans-1,3–dicarboxylate in guinea-pig cerebral cortical slices. J. Neurochem. 58, 1964–1966.PubMedCrossRefGoogle Scholar
  24. Casabona, G., Genazzani, A. A., Di Stefano, M., Sortino, M. A., and Nicoletti, F. (1992) Developmental changes in the modulation of cyclic AMP formation by the metabotropic glutamate receptor agonist 1S,3R-aminocyclopentane- 1,3–dicarboxlic acid in brain slices. J. Neurochem. 59, 1161–1163.PubMedCrossRefGoogle Scholar
  25. Charpak, S., Gähwiler, B. H., Do, K. Q., and Knöpfel, T. (1990) Potassium conductances in hippocampal neurons blocked by excitatory amino-acid transmitters. Nature 347, 765–767.PubMedCrossRefGoogle Scholar
  26. Chavez-Noriega, L. E. and Stevens, C. F. (1992) Modulation of synaptic efficacy inGoogle Scholar
  27. field CA1 of the rat hippocampus by forskolin. Brain Res 574 85–92.Google Scholar
  28. Chuang, D. (1989) Neurotransmitter receptors and phosphoinositide turnover. Ann.Google Scholar
  29. Rev. Pharmacol. Toxicol. 29 71–110.Google Scholar
  30. Chung, D. S., Winder, D. G., and Conn, P. J. (1993) 4–Bromohomoibotenic acid selectively activates an ACPD-insensitive metabotropic glutamate receptor coupled to phosphoinositide hydrolysis in rat cortical slices. J. Neurochem. (in press)Google Scholar
  31. Collins, D. R. and Davies, S. N. (1993) Co-administration of (1S,3R)-1–aminocyclopentane-1,3–dicarboxylic acid and arachidonic acid potentiates synaptic transmission in rat hippocampal slices. Eur. J. Pharmacol. 240, 325, 326.Google Scholar
  32. Conn, P. J. and Desai, M. A. (1991) Pharmacology and physiology of metabotropic glutamate receptors in mammalian central nervous system. Drug Dey. Res. 24, 207–229.CrossRefGoogle Scholar
  33. Curras, M. C. and Dingledine, R. (1992) Selectivity of amino acid transmitters acting at N-methyl-D-aspartate and amino-3–hydroxy-5–methyl-4–isoxazolproprionate receptors. Mol. Pharmacol. 41, 520–526.PubMedGoogle Scholar
  34. Desai, M. A. and Conn, P. J. (1990) Selective activation of phosphoinositide hydrolysis by a rigid analogue of glutamate. Neurosci. Lett. 109, 157–162.PubMedCrossRefGoogle Scholar
  35. Desai, M. A., Smith, T. S., and Conn, P. J. (1992) Multiple metabotropic glutamate receptors regulate hippocampal function. Synapse 12, 206–213.PubMedCrossRefGoogle Scholar
  36. Doble, A. and Perrier, M. L. (1989) Pharmacology of excitatory amino acid receptors coupled to inositol phosphate metabolism in neonatal rat striatum. Neurochem. Int. 15, 1–8.PubMedCrossRefGoogle Scholar
  37. Donaldson, J., Kendall, D. A., and Hill, S. J. (1990) Discriminatory effects of forskolin and EGTA on the indirect cyclic AMP responses to histamine, noradrenaline, 5–hydroxytryptamine, and glutamate in guinea-pig cerebral cortical slices. J. Neurochem. 54, 1484–1491.PubMedCrossRefGoogle Scholar
  38. Dudek, S. M. and Bear, M. F. (1989) A biochemical correlate of the critical period for synaptic modification in the visual cortex. Science 246, 673–675.PubMedCrossRefGoogle Scholar
  39. Dumuis, A., Pin, J. P., Oomagari, K., Sebben, M., and Bockaert, J. (1990) Arachidonic acid released from striatal neurons by joint stimulation of ionotropic and metabotropic quisqualate receptors. Nature 347, 181–183.CrossRefGoogle Scholar
  40. Dumuis, A., Sebben, M., Fagni, L., Prezeau, L., Manzoni, O., Cragoe, E. J., Jr., and Bockaert, J. (1993) Stimulation by glutamate receptors of arachidonic acid release depends on the Na+/Ca2+ exchanger in neuronal cells. Mol. Pharmacol. 43, 976–981.PubMedGoogle Scholar
  41. Dunwiddie, T. V., Taylor, M., Heginbotham, L. R., and Proctor, W. R. (1992) Long-term increases in excitability in the CA1 region of rat hippocampus induced by 13–adrenergic stimulation: possible mediation by cAMP. J. Neurosci. 12, 506–517.PubMedGoogle Scholar
  42. Eaton, S. A., Jane, D. E., Jones, P. L. S. J., Porter, R. H. P., Pook, P. C.-K., Sunter, D. C., Udvarhelyi, P. M., Roberts, P. J., Salt, T. E., and Watkins, J. C. (1993) Competitive antagonism at metabotropic glutamate receptors by (S)-4–carboxyphenylglycine and (RS)-a methyl-4–carboxyphenylglycine. Eur. J. Pharmacol. 244, 195–197.PubMedCrossRefGoogle Scholar
  43. Federman, A. D., Conklin, B. R., Schrader, K. A., Reed, R. R., and Bourne, H. R. (1992) Hormonal stimulation of adenylyl cyclase through Gi-protein 3y subunits. Nature 356, 159–161.PubMedCrossRefGoogle Scholar
  44. Feinstein, P. G., Schrader, K. A., Bakalyar, H. A., Tang, W., Krupinski, J., Gilman, A. G., and Reed, R. R. (1991) Molecular cloning and characterization of a Caz+/ calmodulin-insensitive adenylyl cyclase from rat brain. Proc. Natl. Acad. Sci. USA 88, 10,173–10, 177.Google Scholar
  45. Foster, G. A. and Roberts, P. J. (1980) Pharmacology of excitatory amino acid receptors mediating the stimulation of rat cerebellar cyclic GMP levels in vitro. Life Sci. 27, 215–221.CrossRefGoogle Scholar
  46. Foster, G. A. and Roberts, P. J. (1981) Stimulation of rat cerebellar guanosine 3’,5’-cyclic monophosphate (cyclic GMP) levels: effects of amino acid antagonists. Br. J. Pharmacol. 74, 723–729.PubMedCrossRefGoogle Scholar
  47. Furuya, S., Ohmori, H., Shigemoto, T., and Sugiyama, H. (1989) Intracellular calcium mobilization triggered by a glutamate receptor in rat cultured hippocampal cells. J. Physiol. 414, 539–548.PubMedGoogle Scholar
  48. Garbarg, M. and Schwartz, J. (1988) Synergism between histamine H1– and H2–receptors in the cAMP response in guinea pig brain slices: effects of phorbol esters and calcium. Mol. Pharmacol. 33, 36–43.Google Scholar
  49. Garthwaite, J. and Balazs, R. (1978) Supersensitivity of the cyclic GMP response to glutamate during cerebellar maturation. Nature 275, 328, 329.Google Scholar
  50. Garthwaite, J., Garthwaite, G., Palmer, R. M. J., and Moncada, S. (1989a) NMDA receptor activation induces nitric oxide synthesis from arginine in rat brain slices. Eur. J. Pharmacol. 172, 413–416.PubMedCrossRefGoogle Scholar
  51. Garthwaite, J., Southam, E., and Anderton, M. (1989b) A kainate receptor linked to nitric oxide synthesis from arginine. J. Neurochem. 53, 1952–1954.PubMedCrossRefGoogle Scholar
  52. Genazzani, A. A., Casabona, G., L’Episcopo, M. R., Condorelli, D. F., Dell’Albani, P., Shinozaki, H., and Nicoletti, F. (1993) Characterization of metabotropic glutamate receptors negatively linked to adenylyl cyclase in brain slices. Brain Res. 622, 132–138.PubMedCrossRefGoogle Scholar
  53. Gerber, U. and Gähwiler, B. H. (1992) 4C3HPG (RS-4–carboxy-3–hydroxyphenylglcine), a weak agonist at metabotropic glutamate receptors, occludes the action of trans-ACPD in hippocampus. Eur. J. Pharmacol. 221 401,402.Google Scholar
  54. Gerber, U., Sim, J. A., and Gähwiler, B. H. (1992) Reduction of potassium conductances mediated by metabotropic glutamate receptors in rat CA3 pyramidal cells does not require protein kinase A. Eur. J. Neurosci. 4, 792–797.PubMedCrossRefGoogle Scholar
  55. Gereau, R. W. and Conn, P. J. (1994) A cyclic AMP-dependent form of associative synaptic plasticity induced by coactivation of 13–adrenergic receptors and metabotropic glutamate receptors in rat hippocampus. J. Neurosci. 14, 3310–3318.PubMedGoogle Scholar
  56. Glaum, S. R. and Miller, R. J. (1993a) Zinc protoporphyrin-1X blocks the effects of metabotropic glutamate receptor activation in the rat nucleus tractus solitarius. Mol. Pharmacol. 43, 965–969.PubMedGoogle Scholar
  57. Glaum, S. R. and Miller, R. J. (1993b) Activation of metabotropic glutamate receptor produces reciprocal regulation of ionotropic glutamate and GABA responses in the nucleus of the tractus solitarius of the rat. J. Neurosci. 13 (4), 1636–1641.PubMedGoogle Scholar
  58. Glaum, S. R., Holzwarth, J. A., and Miller, R. J. (1990a) Glutamate receptors activate Cat+ mobilization and Ca’ influx into astrocytes. Proc. Natl. Acad. Sci. USA 87, 3454–3458.PubMedCrossRefGoogle Scholar
  59. Glaum, S. R., Scholz, W. K., and Miller, R. J. (1990b) Acute and long-term glutamate-mediated regulation of [Ca++]i in rat hippocampal pyramidal neurons in vitro. J. Pharmacol. Exp. Ther. 253, 1293–1302.PubMedGoogle Scholar
  60. Godfrey, P. P. and Taghavi, Z. (1990) The effect of non-NMDA antagonists and phorbol esters on excitatory amino acid-stimulated inositol phosphate formation in rat cerebral cortex. Neurochem. Int. 16, 65–72.PubMedCrossRefGoogle Scholar
  61. Goh, J. W. and Ballyk, B. A. (1993) A cAMP-linked metabotropic glutamate receptor in hippocampus. NeuroReport 4, 454–456.PubMedCrossRefGoogle Scholar
  62. Griffiths, R. (1990) Cysteine sulfinate (CSA) as an excitatory amino acid transmitter candidate in the mammalian central nervous system. Prog. Neurobiol. 35, 313–323.PubMedCrossRefGoogle Scholar
  63. Guiramand, J., Vignes, M., and Recasens, M. (1991) A specific transduction mechanism for the glutamate action on phosphoinositide metabolism via the quisqualate metabotropic receptor in rat brain synaptoneurosomes: II. calcium dependency, cadmium inhibition. J. Neurochem. 57, 1501–1509.PubMedCrossRefGoogle Scholar
  64. Haas, H. L. and Gähwiler, B. H. (1992) Vasoactive intestinal polypeptide modulates neuronal excitability in hippocampal slices of the rat. Neurosci. 47 (2), 273–277.CrossRefGoogle Scholar
  65. Harvey, J. and Collingridge, G. L. (1993) Signal transduction pathways involved in the acute potentiation of NMDA responses by 1S,3R-ACPD in rat hippocampal slices. Br. J. Pharmacol. 109, 1085–1090.PubMedCrossRefGoogle Scholar
  66. Heginbotham, L. R. and Dunwiddie, T. V. (1991) Long-term increases in the evoked population spike in the CA1 region of rat hippocampus induced by (3–adrenergic receptor activation. J. Neurosci. 11 (8), 2519–2527.PubMedGoogle Scholar
  67. Herrero, I., Miras-Portugal, M. T., and Sanchez-Prieto, J. (1992) Positive feedback of glutamate exocytosis by metabotropic presynaptic receptor stimulation. Nature 360, 163–166.PubMedCrossRefGoogle Scholar
  68. Hoehn, K. and White, T. D. (1990a) Role of excitatory amino acid receptors in K’-and glutamate-evoked release of endogenous adenosine from rat cortical slices. J. Neurochem. 54, 256–265.PubMedCrossRefGoogle Scholar
  69. Hoehn, K. and White, T. D. (1990b) N-Methyl-D-aspartate, kainate, and quisqualate release endogenous adenosine from rat cortical slices. Neurosci. 39, 441–450.CrossRefGoogle Scholar
  70. Holler, T., Cappel, E., Klein, J., and Löffelholz, K. (1993) Glutamate activates phospholipase D in hippocampal slices of newborn and adult rats. J. Neurochem. 61, 1569–1572.PubMedCrossRefGoogle Scholar
  71. Houamed, K. M., Kuijper, J. L., Gilbert, T. L., Haldeman, B. A., O’Hara, P. J., Mulvihill, E. R., Almers, W., and Hagen, F. S. (1991) Cloning, expression, and gene structure of a G protein-coupled glutamate receptor from rat brain. Science 252, 1318–1321.PubMedCrossRefGoogle Scholar
  72. Hu, G. and Storm, J. F. (1992) 2–Amino-3–phosphonopropionate fails to block postsynaptic effects of metabotropic glutamate receptors in rat hippocampal neurons. Acta. Physiol. Scand. 145, 187–191.Google Scholar
  73. Irving, A. J., Collingridge, G. L., and Schofield, J. G. (1992) L-Glutamate and acetylcholine mobilise Cat+ from the same intracellular pool in cerebellar granule cells using transduction mechanisms with different Ca“ sensitivities. Cell Calcium 13, 293–301.PubMedCrossRefGoogle Scholar
  74. Irving, A. J.., Schofield, J. G., Watkins, J. C., Sunter, D. C., and Collingridge, G. L. (1990)1 S,3R-ACPD stimulates and L-AP3 blocks Ca’ mobilization in rat cerebellar neurons. Eur. J. Pharmacol. 186, 363–365.Google Scholar
  75. Itano, Y., Murayama, T., Kitamura, Y., and Nomura, Y. (1992) Glutamate inhibits adenylate cyclase activity in dispersed rat hippocampal cells directly via an N-methyl-D-aspartate-like metabotropic receptor. J. Neurochem. 59, 822–828.PubMedCrossRefGoogle Scholar
  76. Johnson, R. D. and Minneman, K. P. (1987) Differentiation of a1–adrenergic receptors linked to phosphatidylinositol turnover and and cAMP accumulation in rat brain. Mol. Pharmacol. 31, 239–246.PubMedGoogle Scholar
  77. Knöpfel T., Vranesic I., Gähwiler B. H., and Brown D. A. (1990) Muscarinic and 3adrenergic depression of the slow Cat+-activated potassium conductance in hippocampal CA3 pyramidal cells is not mediated by a reduction of depolarization-induced cytosolic Ca“ transients. Proc. Natl. Acad. Sci. USA 87, 4083–4087.PubMedCrossRefGoogle Scholar
  78. Limbird, L. E. (1988) Receptors linked to inhibition of adenylate cyclase: additional signaling mechanisms. FASEB J. 2, 2686–2695.PubMedGoogle Scholar
  79. Littman, L., Glatt, B. S., and Robinson, M. B. (1993) Multiple subtypes of excitatory amino acid receptors coupled to the hydrolysis of phosphoinositides in rat brain. J. Neurochem. 61, 586–593.PubMedCrossRefGoogle Scholar
  80. Löffelholz, K. (1989) Receptor regulation of choline phospholipid hydrolysis. A novel source of diacylglycerol and phosphatididic acid. Biochem. Pharmacol. 38, 1543–1549.PubMedCrossRefGoogle Scholar
  81. Madison, D. V., Malenka, R. C., and Nicoll, R. A. (1991) Mechanisms underlying long-term potentiation of synaptic transmission. Ann. Rev. Neurosci. 14, 379–397.PubMedCrossRefGoogle Scholar
  82. Magistretti, P. J. and Schorderet, M. (1985) Norepinephrine and histamine potentiate the increases in cyclic adenosine 3’:5’-monophosphate elicited by vasoactive intestinal polypeptide in mouse cerebral cortical slices: mediation by al-adrenergic and HI-histaminergic receptors. J. Neurosci. 5, 362–368.PubMedGoogle Scholar
  83. Manzoni, O., Prezeau, L., Rassendren, F. A., Sladeczek, F., Curry, K., and Bockaert, J. (1992a) Both enantiomers of 1–aminocyclopentyl-1,3–dicarboxylate are full agonists of metabotropic glutamate receptors coupled to phospholipase C. Mol. Pharmacol. 42, 322–327.PubMedGoogle Scholar
  84. Manzoni, O., Prezeau, L., Sladeczek, F., and Bockaert, J. (1992b) Trans-ACPD inhibits cAMP formation via a pertussis toxin-sensitive G-protein. Eur. J. Pharmacol. 225, 357–358.Google Scholar
  85. Manzoni, O., Fagni, L., Pin, J. P., Rassendren, F., Poulat, F., Sladeczek, F., and Bockaert, J. (1990) (trans)-1–Amino-cyclopentyl-1,3–dicarboxylate stimulates quisqualate phosphoinositide-coupled receptors but not ionotropic glutamate receptors in striatal neurons and Xenopus oocytes. Mol. Pharmacol. 38, 1–6.Google Scholar
  86. Manzoni, O. J. J., Poulat, F., Do, E., Sahuquet, A., Sassetti, I., Bockaert, J., and Sladeczek, F. A. J. (1991) Pharmacological characterization of the quisqualate receptor coupled to phospholipase C (Qp) in striatal neurons. Eur. J. Pharmacol. 207, 231–241.Google Scholar
  87. Masu, M. and Nakanishi, S. (1993) Molecular biology of metabotropic glutamate receptors and their physiological function. Functional Neurology 8, 35.Google Scholar
  88. Masu, M., Tanabe, Y., Tsuchida, K., Shigemoto, R., and Nakanishi, S. (1991) Sequence and expression of a metabotropic glutamate receptor. Nature 349, 760–765.PubMedCrossRefGoogle Scholar
  89. McDonough, P. M., Goldstein, D., and Brown, J. H. (1988) Elevation of cytoplasmic calcium concentration stimulates hydrolysis of phosphatidylinositol bisphosphate in chick heart cells: effect of sodium channel activators. Mol. Pharmacol. 33, 310–315.PubMedGoogle Scholar
  90. Milani, D., Facci, L., Buso, M., Toffano, G., Leon, A., and Skaper, S. D. (1990) Excitatory amino acid receptor agonists stimulate membrane inositol phospholipid hydrolysis and increase cytoplasmic free Ca“ in primary cultures of retinal neurons. Cellular Signalling 2, 359–368.PubMedCrossRefGoogle Scholar
  91. Murphy, S. N. and Miller, R. J. (1988) A glutamate receptor regulates Ca’ mobilization in hippocampal neurons. Proc. Natl. Acad. Sci. USA 85, 8737–8741.PubMedCrossRefGoogle Scholar
  92. Murphy, S. N. and Miller, R. J. (1989) Two distinct quisqualate receptors regulate Cat’ homeostasis in hippocampal neurons in vitro. Mol. Pharmacol. 35, 671–680.PubMedGoogle Scholar
  93. Nakagawa, Y., Saitoh, K., Ishihara, T., Ishida, M., and Haruhiko, S. (1990) (25,35,45)a-(carboxyciclopropyl)glycine is a novel agonist of metabotropic glutamate receptors. Eur. J. Pharmacol. 184, 205–206.Google Scholar
  94. Nakajima, Y., Iwakabe, H., Akazawa, C., Nawa, H., Shigemoto, R., Mizuno, N., and Nakanishi, S. (1993) Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2–amino-4phosphonobutyrate. J. Biol. Chem. 268, 11868–11873.PubMedGoogle Scholar
  95. Nicoletti, F., Iadarola, M. F., Wroblewski, J. T., and Costa, E. (1986a) Excitatory amino acid recognition sites coupled with inositol phospholipid metabolism: Developmental changes and interaction with al-adrenoreceptors. Proc. Natl. Acad. Sci. USA 83, 1931–1935.PubMedCrossRefGoogle Scholar
  96. Nicoletti, F., Meek, J. L., Iadarola, M. J., Chuang, D. M., Roth, B. L., and Costa, E. (1986b) Coupling of inositol phospholipid metabolism with excitatory amino acid recognition sites in rat hippocampus. J. Neurochem. 46, 40–46.PubMedCrossRefGoogle Scholar
  97. Nicoletti, F., Wroblewski, J. T., Fadda, E., and Costa, E. (1988) Pertussis toxin inhibits signal transduction at a specific metabolotropic glutamate receptor in primary cultures of cerebellar granule cells. Neuropharmacol. 27, 551–556.CrossRefGoogle Scholar
  98. Nicoletti, F., Magri, G., Ingrao, F., Bruno, V., Catania, M. V., Dell’Albani, P., Condorelli, D. F., and Avola, R. (1990) Excitatory amino acids stimulate inositol phospholipid hydrolysis and reduce proliferation in cultured astrocytes. J. Neurochem. 54, 771–777.PubMedCrossRefGoogle Scholar
  99. Okada, D. (1992) Two pathways of cyclic GMP production through glutamate receptor-mediated nitric oxide synthesis. J. Neurochem. 59, 1203–1210.PubMedCrossRefGoogle Scholar
  100. Ormandy, G. C. (1992) Inhibition of excitatory amino acid-stimulated phosphoinositide hydrolysis in rat hippocampus by L-aspartate- 3–hydroxamate. Brain Res. 572, 103–107.PubMedCrossRefGoogle Scholar
  101. Palmer, E., Monaghan, D. T., and Cotman, C. W. (1988) Glutamate receptors and phosphoinositide metabolism: stimulation via quisqualate receptors is inhibited by N-methyl-D-aspartate receptor activation. Mol. Brain Res. 4, 161–165.CrossRefGoogle Scholar
  102. Palmer, E., Monaghan, D. T., and Cotman, C. W. (1989) Trans-ACPD, a selective agonist of the phosphoinositide-coupled excitatory amino acid receptor. Eur. J. Pharmacol. 166, 585–587.PubMedCrossRefGoogle Scholar
  103. Palmer, E., Nangel-Taylor, K., Krause, J. D., Roxas, A., and Cotman, C. W. (1990) Changes in excitatory amino acid modulation of phosphoinositide metabolism during development. Dey. Brain Res. 51, 132–134.CrossRefGoogle Scholar
  104. Park, T. S. and Gidday, J. M. (1990) Effect of dipyridamole on cerebral extracellularGoogle Scholar
  105. adenosine level in vivo. J. Cereb. Blood Flow Metab. 10 424–427.Google Scholar
  106. Patel, J., Keith, R. A., Salama, A. I., and Moore, W. C. (1991) Role of calcium in regulation of phosphoinositide signaling pathway. J. Mol. Neurosci. 3, 19–27.PubMedCrossRefGoogle Scholar
  107. Patel, J., Moore, W. C., Thompson, C., Keith, R. A., and Salama, A. I. (1990) Characterization of the quisqualate receptor linked to phosphoinositide hydrolysis in neurocortical cultures. J. Neurochem. 54, 1461–1466.PubMedCrossRefGoogle Scholar
  108. Pearce, B., Morrow, C., and Murphy, S. (1990) Further characterisation of excitatory amino acid receptors coupled to phosphoinositide metabolism in astrocytes. Neurosci. Lett. 113, 298–303.PubMedCrossRefGoogle Scholar
  109. Pilc, A. and Enna, S. J. (1986) Activation of a2–adrenergic receptors augments neurotransmitter-stimulated cyclic AMP accumulation in rat brain cerebral cortical slices. J. Pharmacol. Exp. Ther. 237, 725–730.Google Scholar
  110. Porter, P. H. P. and Roberts, P. J. (1993) Glutamate metabotropic receptor activation in neonatal rat cerebral cortex by sulphur-containing excitatory amino acids. Neurosci. Lett. 154, 78–80.PubMedCrossRefGoogle Scholar
  111. Porter, R. H. P., Briggs, R. S. J., and Roberts, P. J. (1992) L-Aspartate-13–hydroxamate exhibits mixed agonist/antagonist activity at the glutamate metabotropic receptor in rat neonatal cerebrocortial slices. Neurosci. Lett. 144, 87–89.PubMedCrossRefGoogle Scholar
  112. Prezeau, L., Manzoni, O., Homburger, V., Sladeczek, F., Curry, K., and Bockaert, J. (1992) Characterization of a metabotropic glutamate receptor: direct negative coupling to adenylyl cyclase and involvement of a pertussis toxin-sensitive G protein. Proc. Natl. Acad. Sci. USA 89, 8040–8044.PubMedCrossRefGoogle Scholar
  113. Pullan, L. M., Olney, J. W., Price, M. T., Compton, R. P., Hood, W. F., Michel, J., and Monahan, J. B. (1987) Excitatory amino acid receptor potency and subclass specificity of sulfur-containing amino acids. J. Neurochem. 49, 1301–1307.PubMedCrossRefGoogle Scholar
  114. Rana, R. S. and Hokin, L. E. (1990) Role of phosphoinositides in transmembrane signalling. Physiological Rev. 70, 115–164.Google Scholar
  115. Recasens, M., Guiramand, J., Nourigat, A., Sassetti, I., and Devilliers, G. (1988) A new quisqualate receptor subtype (sAA2) responsible for the glutamate-induced inositol phosphate formation in rat brain synaptoneurosomes. Neurochem. Int. 13, 463–467.PubMedCrossRefGoogle Scholar
  116. Recasens, M., Varga, V., Nanopoulos, D., Saadoun, F., Vincendon, G., andBenavides, J. (1982) Evidence for cysteine sulfinate as a neurotransmitter. Brain Res. 239, 153–173.PubMedCrossRefGoogle Scholar
  117. Robertson, P. L., Bruno, G. R., and Datta, S.C. (1990) Glutamate-stimulated, guanine nucleotide-mediated phosphoinositide turnover in astrocytes is inhibited by cyclic AMP. J. Neurochem. 55, 1727–1733.PubMedCrossRefGoogle Scholar
  118. Schaad, N. C., Schorderet, M., and Magistretti, P. J. (1989) Accumulation of cyclic AMP elicited by vasoactive intestinal peptide is potentiated by noradrenaline, histamine, adenosine, baclofen, phorbol esters, and ouabain in mouse cerebral slices: studies on the role of arachadonic acid metabolites and protein kinase. J. Neurochem. 53, 1941–1951.PubMedCrossRefGoogle Scholar
  119. Schmidt, M. J., Thornberry, J. F., and Molloy, B. B. (1977) Effects of kainate and other glutamate analogues on cyclic nucleotide accumulation in slices of rat cerebellum. Brain Res. 121, 182–189.PubMedCrossRefGoogle Scholar
  120. Schoepp, D. D. and Hillman, C. C., Jr. (1990) Developmental and pharmacological characterization of quisqualate, ibotenate and trans-1–amino-1,3–cyclopentanedicarboxylic acid stimulations of phosphoinositide hydrolysis in rat cortical brain slices. Biogenic Amines 7, 331–340.Google Scholar
  121. Schoepp, D. D. and Johnson, B. G. (1988) Excitatory amino acid agonist-antagonist interactions at 2–amino-4–phosphonobutyric acid-sensitive quisqualate receptors coupled to phosphoinositide hydrolysis in slices of rat hippocampus. J. Neurochem. 50, 1605–1613.PubMedCrossRefGoogle Scholar
  122. Schoepp, D. D. and Johnson, B. G. (1989a) Inhibition of excitatory amino acid-stimulated phosphoinositide hydrolysis in the neonatal rat hippocampus by 2–amino-3–phosphonopropionate. J. Neurochem. 53, 1865–1870.PubMedCrossRefGoogle Scholar
  123. Schoepp, D. D. and Johnson, B. G. (1989b) Comparison of excitatory amino acid-stimulated phosphoinositide hydrolysis and N-[3H] Acetylaspartylglutamate binding in rat brain: selective inhibition of phosphoinositide hydrolysis by 2–amino-3–phosphonopropionate. J. Neurochem. 53, 273–278.PubMedCrossRefGoogle Scholar
  124. Schoepp, D. D. and Johnson, B. G. (1993) Pharmacology of metabotropic glutamate receptor inhibition of cyclic AMP formation in the adult rat hippocampus. Neurochem. Int. 22, 277–283.PubMedCrossRefGoogle Scholar
  125. Schoepp, D. D., Johnson, B. G., and Monn, J. M. (1992a) Inhibition of cyclic AMP formation by a selective metabotropic glutamate receptor agonist. J. Neurochem. 58, 1184–1186.PubMedCrossRefGoogle Scholar
  126. Schoepp, D. D., Johnson, B. G., Sacaan, A. I., True, R. A., and Monn, J. A. (1992b) In vitro and in vivo pharmacology of 1S,3R-and 1R,3S-ACPD: evidence for a role of metabotropic glutamate receptors in striatal motor function. Mol. Neuropharmacol. 2, 33–37.Google Scholar
  127. Schoepp, D. D., Johnson, B. G., True, R. A., and Monn, J. A. (1991) Comparison of (1S,3R)-1–aminocyclopentane-1,3–dicarboxylic acid (1S,3R-ACPD)-and 1R,3S- ACPD-stimulated brain phosphoinositide hydrolysis. Eur. J. Pharmacol. -Mol. Pharmacol. 207, 351–353.CrossRefGoogle Scholar
  128. Scholz, W. K. and Palfrey, H. C. (1991) Glutamate-stimulated protein phosphorylation in cultured hippocampal pyramidal neurons. J. Neurosci. 11 (8), 2422–2432.PubMedGoogle Scholar
  129. Slack, J. R. and Pockett, S. (1991) Cyclic AMP induces long-term increase in synaptic efficacy in CA1 region of rat hippocampus. Neurosci. Lett. 130, 69–70.PubMedCrossRefGoogle Scholar
  130. Sladeczek, F., Pin, J. P., Recasens, M., Bockaert, J., and Weiss, S. (1985) Glutamate stimulates inositol phosphate formation in striatal neurons. Nature 317, 717, 718.Google Scholar
  131. Sortino, M. A., Nicoletti, F., and Canonico, P. L. (1991) Metabotropic glutamate receptors in rat hypothalamus characterization and developmental profile. Dey. Brain Res. 61, 169–172.CrossRefGoogle Scholar
  132. Stratton, K. R., Worley, P. F., and Baraban, J. M. (1990) Pharmacological characterization of phosphoinositide-linked glutamate receptor excitation of hippocampal neurons. Eur. J. Pharmacol. 186, 357–361.PubMedCrossRefGoogle Scholar
  133. Sugiyama, H., Ito, I., and Hirono, C. (1987) A new type of glutamate receptor linked to inositol phospholipid metabolism. Nature 325, 531–533.PubMedCrossRefGoogle Scholar
  134. Sugiyama, H., Ito, I., and Watanabe, M. (1989) Glutamate receptor subtypes may be classified into two major categories: a study of Xenopus oocytes injected with rat brain mRNA. Neuron 3, 129–132.PubMedCrossRefGoogle Scholar
  135. Tanabe, Y., Masu, M., Ishii, T., Shigemoto, R., and Nakanishi, S. (1992) A family of metabotropic glutamate receptors. Neuron 8, 169–179.PubMedCrossRefGoogle Scholar
  136. Tanabe, Y., Nomura, A., Masu, M., Shigemotor, R., Mizuno, N., and Nakanishi, S. (1993) Signal transduction, pharmacological properties, and expression patterns of two rat metabotropic glutamate receptors, mGluR3 and mGluR4. J. Neurosci. 13, 1372–1378.PubMedGoogle Scholar
  137. Tang, W.-J. and Gilman, A. G. (1991) Type-specific regulation of adenlyl cyclase by G protein 3y subunits. Science 254, 1500–1503.PubMedCrossRefGoogle Scholar
  138. Trombley, P. Q. and Westbrook, G. L. (1992) L-AP4 inhibits calcium currents and synaptic transmission via a G-protein-coupled glutamate receptor. J. Neurosci. 12, 2043–2050.PubMedGoogle Scholar
  139. Thomsen, C., Kristensen, P., Mulvihill, E., Haldeman, B., and Suzdak, P. D. (1992) L-2–amino-4–phosphonobutyrate (L-AP4) is an agonist at the type IV metabotropic glutamate receptor which is negatively coupled to adenylate cyclase. Eur. J. Pharmacol. 227, 361–362.PubMedCrossRefGoogle Scholar
  140. Thomsen, C. and Suzdak, P. D. (1993) 4–carboxy-3–hydroxyphenylglycine, an antagonist at type I metabotropic glutamate receptors. Eur. J. Pharmacol. 245, 299–301.Google Scholar
  141. Verdoorn, T. A. and Dingledine, R. (1988) Excitatory amino acid receptors expressed in Xenopus oocytes: agonist pharmacology. Mol. Pharmacol. 34, 298–307.PubMedGoogle Scholar
  142. Verma, A., Hirsch, D. J., Glatt, G. V., Ronnett, G. V., and Snyder, S. H. (1993) Carbon monoxide: a putative neural messenger. Science 259, 381–384.PubMedCrossRefGoogle Scholar
  143. Weiss, S. (1989) Two distinct quisqualate receptor systems are present on striatal neurons. Brain Res. 491, 189–193.PubMedCrossRefGoogle Scholar
  144. Winder, D. G. and Conn, P. J. (1992) Activation of metabotropic glutamate receptors in the hippocampus increases cyclic AMP accumulation. J. Neurochem. 59, 375–378.PubMedCrossRefGoogle Scholar
  145. Winder, D. G. and Conn, P. J. (1993) Activation of metabotropic glutamate receptors increases cAMP accumulation in hippocampus by potentiating responses to endogenous adenosine. J. Neurosci. 13, 38–44.PubMedGoogle Scholar
  146. Winder, D. G., Smith, T. S., and Conn, P. J. (1993) Pharmacological differentiation of metabotropic glutamate receptors coupled to potentiation of cAMP responses and phosphoinositide hydrolysis. J. Pharmacol. Exp. Ther. 266, 518–525.PubMedGoogle Scholar
  147. Wood, P. L., Emmett, M. R., Rao, T. S., Cler, J., Mick, S., and Iyengar, S. (1990) Inhibition of nitric oxide synthase blocks N-methyl-D-aspartate-, quisqualate-, kainate-, harmaline-, and pentylenetetrazole-dependent increases in cerebellar cyclic GMP in vivo. J. Neurochem. 55, 346–348.PubMedCrossRefGoogle Scholar
  148. Wroblewska, B., Wroblewski, J. T., Saab, O. H., and Neale, J. H. (1993) N-acetylaspartylglutamate inhibits forskolin-stimulated cyclic AMP levels via a metabotropic glutamate receptor in cultured cerebellar granule cells. J. Neurochem. 61, 943–948.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • P. Jeffrey Conn
  • Valerie Boss
  • Dorothy S. Chung

There are no affiliations available

Personalised recommendations