Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1992 Jan;105(1):83–86. doi: 10.1111/j.1476-5381.1992.tb14214.x

Effects of acromelic acid A on the binding of [3H]-kainic acid and [3H]-AMPA to rat brain synaptic plasma membranes.

A L Smith 1, R A McIlhinney 1
PMCID: PMC1908608  PMID: 1375859

Abstract

1. The ability of acromelic acid A to inhibit [3H]-kainic acid and [3H]-(RS)-alpha-amino-3-hydroxy-5-methyloxazole-4-propionic acid ([3H]-AMPA) binding to rat brain synaptic plasma membranes was investigated by equilibrium radioligand binding assay. 2. Kinetic analysis of [3H]-kainic acid binding demonstrated the existence of two kainate binding sites in this tissue preparation and yielded equilibrium dissociation constants for [3H]-kainic acid of KD = 0.4 nM and KD = 20.8 nM. 3. Kainic acid and domoic acid both appeared to displace [3H]-kainic acid from a single binding site with equilibrium binding constants of KD = 19.4 nM and Ki = 14.5 nM respectively. Acromelic acid A exhibited a biphasic inhibition of [3H]-kainic acid binding to synaptic membranes with binding affinities of Ki = 15.1 nM and Ki = 1.49 microM. 4. In the absence of chaotropic ions, the order of potency of inhibition of [3H]-AMPA binding was acromelic acid A (Ki = 26 nM) greater than AMPA (KD = 184 nM) greater than domoic acid (Ki = 499 nM). 5. The inclusion of 100 mM thiocynanate ion in the [3H]-AMPA binding assay resulted in a change in the order of potency to: AMPA (KD = 160 nM) greater than acromelic acid A (Ki = 289 nM) greater than domoic acid (Ki = 9.02 microM). 6. These results show that acromelic acid A distinguishes two kainate binding sites in rat brain synaptic plasma membranes and in addition, that in the absence of chaotropic ions, acromelic acid A is the most potent displacer of [3H]-AMPA binding yet described.

Full text

PDF
83

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ambrosini A., Henley J. H., Barnard E. A. Kainate and quisqualate binding sites are co-purified from Xenopus central nervous system. Biochem Soc Trans. 1990 Jun;18(3):401–402. doi: 10.1042/bst0180401. [DOI] [PubMed] [Google Scholar]
  2. Gregor P., Mano I., Maoz I., McKeown M., Teichberg V. I. Molecular structure of the chick cerebellar kainate-binding subunit of a putative glutamate receptor. Nature. 1989 Dec 7;342(6250):689–692. doi: 10.1038/342689a0. [DOI] [PubMed] [Google Scholar]
  3. Henley J. M., Ambrosini A., Krogsgaard-Larsen P., Barnard E. A. Evidence for a single glutamate receptor of the ionotropic kainate/quisqualate type. New Biol. 1989 Nov;1(2):153–158. [PubMed] [Google Scholar]
  4. Hollmann M., O'Shea-Greenfield A., Rogers S. W., Heinemann S. Cloning by functional expression of a member of the glutamate receptor family. Nature. 1989 Dec 7;342(6250):643–648. doi: 10.1038/342643a0. [DOI] [PubMed] [Google Scholar]
  5. Honoré T., Drejer J., Nielsen M. Calcium discriminates two [3H]kainate binding sites with different molecular target sizes in rat cortex. Neurosci Lett. 1986 Mar 28;65(1):47–52. doi: 10.1016/0304-3940(86)90118-7. [DOI] [PubMed] [Google Scholar]
  6. Ishida M., Shinozaki H. Acromelic acid is a much more potent excitant than kainic acid or domoic acid in the isolated rat spinal cord. Brain Res. 1988 Dec 6;474(2):386–389. doi: 10.1016/0006-8993(88)90456-8. [DOI] [PubMed] [Google Scholar]
  7. Jones D. H., Matus A. I. Isolation of synaptic plasma membrane from brain by combined flotation-sedimentation density gradient centrifugation. Biochim Biophys Acta. 1974 Aug 9;356(3):276–287. doi: 10.1016/0005-2736(74)90268-5. [DOI] [PubMed] [Google Scholar]
  8. Keinänen K., Wisden W., Sommer B., Werner P., Herb A., Verdoorn T. A., Sakmann B., Seeburg P. H. A family of AMPA-selective glutamate receptors. Science. 1990 Aug 3;249(4968):556–560. doi: 10.1126/science.2166337. [DOI] [PubMed] [Google Scholar]
  9. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  10. London E. D., Coyle J. T. Specific binding of [3H]kainic acid to receptor sites in rat brain. Mol Pharmacol. 1979 May;15(3):492–505. [PubMed] [Google Scholar]
  11. Maruyama M., Takeda K. Effects of acromelic acid A on the binding of [3H]glutamic acid and [3H]kainic acid to synaptic membranes and on the depolarization at the frog spinal cord. Brain Res. 1989 Dec 18;504(2):328–331. doi: 10.1016/0006-8993(89)91379-6. [DOI] [PubMed] [Google Scholar]
  12. Munson P. J., Rodbard D. Ligand: a versatile computerized approach for characterization of ligand-binding systems. Anal Biochem. 1980 Sep 1;107(1):220–239. doi: 10.1016/0003-2697(80)90515-1. [DOI] [PubMed] [Google Scholar]
  13. Olsen R. W., Szamraj O., Houser C. R. [3H]AMPA binding to glutamate receptor subpopulations in rat brain. Brain Res. 1987 Feb 3;402(2):243–254. doi: 10.1016/0006-8993(87)90030-8. [DOI] [PubMed] [Google Scholar]
  14. Slevin J. T., Collins J. F., Coyle J. T. Analogue interactions with the brain receptor labeled by [3H]kainic acid. Brain Res. 1983 Apr 11;265(1):169–172. doi: 10.1016/0006-8993(83)91351-3. [DOI] [PubMed] [Google Scholar]
  15. Wada K., Dechesne C. J., Shimasaki S., King R. G., Kusano K., Buonanno A., Hampson D. R., Banner C., Wenthold R. J., Nakatani Y. Sequence and expression of a frog brain complementary DNA encoding a kainate-binding protein. Nature. 1989 Dec 7;342(6250):684–689. doi: 10.1038/342684a0. [DOI] [PubMed] [Google Scholar]
  16. Watkins J. C., Krogsgaard-Larsen P., Honoré T. Structure-activity relationships in the development of excitatory amino acid receptor agonists and competitive antagonists. Trends Pharmacol Sci. 1990 Jan;11(1):25–33. doi: 10.1016/0165-6147(90)90038-a. [DOI] [PubMed] [Google Scholar]
  17. Wenthold R. J., Hunter C., Wada K., Dechesne C. J. Antibodies to a C-terminal peptide of the rat brain glutamate receptor subunit, GluR-A, recognize a subpopulation of AMPA binding sites but not kainate sites. FEBS Lett. 1990 Dec 10;276(1-2):147–150. doi: 10.1016/0014-5793(90)80529-r. [DOI] [PubMed] [Google Scholar]
  18. Young A. B., Fagg G. E. Excitatory amino acid receptors in the brain: membrane binding and receptor autoradiographic approaches. Trends Pharmacol Sci. 1990 Mar;11(3):126–133. doi: 10.1016/0165-6147(90)90199-i. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES