Skip to main content
Log in

Characterization of two central AMPA-preferring receptors having distinct location, function and pharmacology

  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

The existence of a pharmacological heterogeneity among the glutamate receptors sensitive to (RS)-α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) has been investigated in the adult rat central nervous system (CNS). AMPA stimulated [3H]noradrenaline ([3H]NA) release from hippocampal synaptosomes (pD2 = 4.58) and the production of cGMP in cerebellar slices (pD2 = 7.75). The AMPA effects in the two systems were tested against several glutamate receptor antagonists including 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), 6,7-dinitro-quinoxaline-2,3-dione (DNQX),l-glutamate diethylester (GDEE), γ-d-glutamyl-glycine (GDGG) and γ-d-glutamyl-aminomethylsulphonate (GAMS). In both systems the AMPA effect was equally sensitive to CNQX or DNQX. However, while the AMPA-evoked increase of [3H]NA release from presynaptic terminals was not affected by GAMS, GDGG or GDEE, the postsynaptic cGMP response was prevented by GDGG and GDEE. It is concluded that rat hippocampus and cerebellum possess, respectively, presynaptic and post-synaptic AMPA-sensitive receptors involved in different functions and endowed with diverse pharmacological properties.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bettler B, Boulter J, Hermans-Borgmeyer I, O'Shea-Greenfield A, Deneris ES, Moll C, Borgmeyer U, Hollmann M, Heinemann S (1990) Cloning of a novel glutamate receptor subunit, GluR5: expression in the nervous system during development. Neuron 5:583–595

    Article  PubMed  CAS  Google Scholar 

  • Bettler B, Egebjerg J, Sharma G, Pecht G, Hermans-Borgmeyer I, Moll C, Stevens CF, Heinemann S (1992) Cloning of a putative glutamate receptor: a low affinity kainate-binding subunit. Neuron 8:257–265

    Article  PubMed  CAS  Google Scholar 

  • Boulter J, Hollmann M, O'Shea-Greenfield A, Hartley M, Deneris E, Maron C, Heinemann S (1990) Molecular cloning and functional expression of glutamate receptor subunit genes. Science 249:1033–1037

    Article  PubMed  CAS  Google Scholar 

  • Bradford MM (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  • Bredt DS, Snyder SH (1991) Nitric oxide, a novel neuronal messenger. Neuron 8:3–11

    Article  Google Scholar 

  • Burnashev N, Monyer H, Seeburg PH, Sakmann B (1992) Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Neuron 8:189–198

    Article  PubMed  CAS  Google Scholar 

  • Drejer J, Honoré T (1988) New quinoxalinediones show potent antagonism of quisqualate responses in cultured mouse cortical neurons. Neurosci Lett 87:104–108

    Article  PubMed  CAS  Google Scholar 

  • Egebjerg J, Bettler B, Hermans-Borgmeyer I, Heinemann S (1991) Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA. Nature 351:745–748

    Article  PubMed  CAS  Google Scholar 

  • Garthwaite J (1991) Glutamate, nitric oxide and cell-cell signalling in the nervous system. Trends Neurosci 14:60–67

    Article  PubMed  CAS  Google Scholar 

  • Gray EG, Whittaker VP (1962) The isolation of nerve endings from brain: an electron microscopic study of cell fragments derived by homogenization and centrifugation. J Anat 96:79–87

    PubMed  CAS  Google Scholar 

  • Hall JM, Caulfield MP, Watson SP, Guard S (1993) Receptor subtypes or species homologues: relevance to drug discovery. Trends Pharmacol Sci 14:376–383

    Article  PubMed  CAS  Google Scholar 

  • Herb A, Burnashev N, Werner P, Sakmann B, Wisden W, Seeburg PH (1992) The KA-2 subunit of excitatory amino acid receptors shows widespread expression in brain and forms ion channels with distantly related subunits. Neuron 8:775–785

    Article  PubMed  CAS  Google Scholar 

  • Hollmann M, Hartley M, Heinemann S (1991) Ca2+ permeability of KA-AMPA-gated glutamate receptor channels depends on subunit composition. Science 252:851–853

    Article  PubMed  CAS  Google Scholar 

  • Jones AW, Smith DAS, Watkins JC (1984) Structure-activity relations of dipeptide antagonists of excitatory amino acids. Neuroscience 13:573–581

    Article  PubMed  CAS  Google Scholar 

  • Keinanen K, Wisden W, Sommer B, Werner P, Herb A, Verdoorn TA, Sakmann B, Seeburg PH (1990) A family of AMPA-selective glutamate receptors. Science 249:556–560

    Article  PubMed  CAS  Google Scholar 

  • Lazareno S, Birdsall NJM (1993) Estimation of antagonist Kb from inhibition curves in functional experiments: alternative to the Cheng-Prusoff equation. Trends Pharmacol Sci 14:237–239

    Article  PubMed  CAS  Google Scholar 

  • McLennan H (1975) Excitatory amino acid receptors in the central nervous system. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology, vol 4. Plenum, New York, pp 211–228

    Google Scholar 

  • Pin J-P, Van Vliet BJ, Bockaert J (1989) Complex interaction between quisqualate and kainate receptors as revealed by measurement of GABA release from striatal neurons in primary culture. Eur J Pharmacol Mol Pharmacol Sect 172:81–91

    Article  CAS  Google Scholar 

  • Raiteri M, Angelini F, Levi G (1974) A simple apparatus for studying the release of neurotransmitters from synaptosomes. Eur J Pharmacol 25:411–414

    Article  PubMed  CAS  Google Scholar 

  • Raiteri M, Bonanno G, Marchi M, Maura G (1984) Is there a functional linkage between neurotransmitter uptake mechanisms and presynaptic receptors? J Pharmacol Exp Ther 231:671–677

    PubMed  CAS  Google Scholar 

  • Raiteri M, Garrone B, Pittaluga A (1992) N-Methyl-D-aspartic acid (NMDA) and non-NMDA receptors regulating hippocampal norepinephrine release. II. Evidence for functional cooperation and for coexistence on the same axon terminal. J Pharmacol Exp Ther 260:238–242

    PubMed  CAS  Google Scholar 

  • Seeburg PH (1993) The TiPS/TINS Lecture: the molecular biology of mammalian glutamate receptor channels. Trends Pharmacol Sci 14:297–303

    Article  PubMed  CAS  Google Scholar 

  • Southam E, East SJ, Garthwaite J (1991) Excitatory amino acid receptors coupled to the nitric oxide/cyclic GMP pathway in rat cerebellum during development. J Neurochem 56:2072–2081

    Article  PubMed  CAS  Google Scholar 

  • Werner P, Voigt M, Keinänen K, Wisden W, Seeburg PH (1991) Cloning of a putative high-affinity kainate receptor expressed predominantly in hippocampal CA3 cells. Nature 351:742–744

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Correspondence to: M. Raiteri at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pittaluga, A., Thellung, S., Maura, G. et al. Characterization of two central AMPA-preferring receptors having distinct location, function and pharmacology. Naunyn-Schmiedeberg's Arch. Pharmacol. 349, 555–558 (1994). https://doi.org/10.1007/BF01258458

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01258458

Key words

Navigation