Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1975 Jun;54(2):181–188. doi: 10.1111/j.1476-5381.1975.tb06927.x

Characterization of an inhibitory receptor in rat hippocampus

A microiontophoretic study using conformationally restricted amino acid analogues

M Segal, K Sims, E Smissman
PMCID: PMC1666657  PMID: 1148508

Abstract

1 Pyramidal cells in rat hippocampus were used to study the molecular dimensions of a receptor for inhibitory amino acids in the central nervous system. The inhibitory potencies of γ-aminobutyrate (GABA), β-alanine and glycine were compared by standard microiontophoretic techniques. Subsequently, rigid cyclopentane and cyclohexane amino acid analogues were applied by iontophoresis and their relative efficacies were compared with those of the naturally occurring amino acids.

2 GABA was the most effective of the small aliphatic amino acids in producing inhibition of the firing of hippocampal pyramidal neurones. β-Alanine was less effective and glycine was the least effective. GABA-induced inhibition was antagonized by concurrent iontophoresis of picrotoxin or bicuculline, whereas strychnine did not antagonize GABA inhibition.

3 The ability of the series of substituted aminocyclopentane and aminocyclohexane carboxylic acids to produce inhibition of pyramidal cells was a direct function of the separation of amino and carboxylic acid groups. In both series of the cyclic amino acids the most potent inhibition was demonstrated when the spatial separation was similar to that of the extended GABA molecule (4.74 Å). Additionally, the inhibition of hippocampal pyramidal cells by (±-cis-3-amino-cyclopentanecarboxylic acid, like that produced by GABA, could be blocked by simultaneous application of picrotoxin or bicuculline, but not by strychnine.

4 The present results suggest that the physiologically active conformation of GABA is the fully extended molecule, and additionally indicate that one dimension of the postsynaptic receptor site is within the range of 4.2 to 4.8 ångströms.

Full text

PDF
181

Selected References

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

  1. ANDERSEN P., ECCLES J. C., LOYNING Y. PATHWAY OF POSTSYNAPTIC INHIBITION IN THE HIPPOCAMPUS. J Neurophysiol. 1964 Jul;27:608–619. doi: 10.1152/jn.1964.27.4.608. [DOI] [PubMed] [Google Scholar]
  2. Beart P. M., Curtis D. R., Johnston G. A. 4-aminotetrolic acid: new conformational-restricted analogue of -aminobutyric acid. Nat New Biol. 1971 Nov 17;234(46):80–81. doi: 10.1038/newbio234080a0. [DOI] [PubMed] [Google Scholar]
  3. Beart P. M., Johnston G. A., Uhr M. L. Competitive inhibition of GABA uptake in rat brain slices by some GABA analogues of restricted conformation. J Neurochem. 1972 Aug;19(8):1855–1861. doi: 10.1111/j.1471-4159.1972.tb01474.x. [DOI] [PubMed] [Google Scholar]
  4. Beers W. H., Reich E. Structure and activity of acetylcholine. Nature. 1970 Dec 5;228(5275):917–922. doi: 10.1038/228917a0. [DOI] [PubMed] [Google Scholar]
  5. Curtis D. R., Duggan A. W., Felix D., Johnston G. A. Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord of the cat. Brain Res. 1971 Sep 10;32(1):69–96. doi: 10.1016/0006-8993(71)90156-9. [DOI] [PubMed] [Google Scholar]
  6. Curtis D. R., Felix D., McLellan H. GABA and hippocampal inhibition. Br J Pharmacol. 1970 Dec;40(4):881–883. doi: 10.1111/j.1476-5381.1970.tb10663.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Curtis D. R., Hösli L., Johnston G. A., Johnston I. H. The hyperpolarization of spinal motoneurones by glycine and related amino acids. Exp Brain Res. 1968;5(3):235–258. doi: 10.1007/BF00238666. [DOI] [PubMed] [Google Scholar]
  8. Galindo A. GABA-picrotoxin interaction in the mammalian central nervous system. Brain Res. 1969 Aug;14(3):763–767. doi: 10.1016/0006-8993(69)90220-0. [DOI] [PubMed] [Google Scholar]
  9. Geller H. M., Woodward D. J. An improved constant current source for micro-iontophoretic drug application studies. Electroencephalogr Clin Neurophysiol. 1972 Oct;33(4):430–432. doi: 10.1016/0013-4694(72)90125-3. [DOI] [PubMed] [Google Scholar]
  10. Gilardi R. D. Configuration and conformation of bicuculline, a GABA antagonist. Nat New Biol. 1973 Sep 19;245(142):86–88. doi: 10.1038/newbio245086a0. [DOI] [PubMed] [Google Scholar]
  11. Herz A., Nacimiento A. C. Uber die Wirkung von Pharmaka auf Neurone des Hippocampus nach mikroelektrophoretischer Verabfolgung. Naunyn Schmiedebergs Arch Exp Pathol Pharmakol. 1965 Jul 26;251(3):295–314. [PubMed] [Google Scholar]
  12. Hoffer B. J., Neff N. H., Siggins G. R. Microiontophoretic release of norepinephrine from micropipettes. Neuropharmacology. 1971 Mar;10(21):175–180. doi: 10.1016/0028-3908(71)90038-4. [DOI] [PubMed] [Google Scholar]
  13. New R. R., Richards W. G. Molecular orbital study of hapten-antibody interactions. Nat New Biol. 1972 Jun 14;237(76):214–214. doi: 10.1038/newbio237214a0. [DOI] [PubMed] [Google Scholar]
  14. Obata K., Ito M., Ochi R., Sato N. Pharmacological properties of the postsynaptic inhibition by Purkinje cell axons and the action of gamma-aminobutyric acid on deiters NEURONES. Exp Brain Res. 1967;4(1):43–57. doi: 10.1007/BF00235216. [DOI] [PubMed] [Google Scholar]
  15. Salmoiraghi G. C., Weight F. Micromethods in neuropharmacology: an approach to the study of anesthetics. Anesthesiology. 1967 Jan-Feb;28(1):54–64. [PubMed] [Google Scholar]
  16. Segal M., Bloom F. E. The action of norepinephrine in the rat hippocampus. I. Iontophoretic studies. Brain Res. 1974 May 31;72(1):79–97. doi: 10.1016/0006-8993(74)90652-0. [DOI] [PubMed] [Google Scholar]
  17. Segal M., Sims K., Maggiora L., Smissman E. Analogues of gamma-aminobutyrate on rat hippocampal neurones. Nat New Biol. 1973 Sep 19;245(142):88–89. doi: 10.1038/newbio245088b0. [DOI] [PubMed] [Google Scholar]
  18. Steward E. G., Player R., Quilliam J. P., Brown D. A., Pringle M. J. Molecular conformation of GABA. Nat New Biol. 1971 Sep 15;233(37):87–88. doi: 10.1038/newbio233087a0. [DOI] [PubMed] [Google Scholar]
  19. Van Gelder N. M. Molecular arrangement for physiological action of glutamic acid and gamma-aminobutyric acid. Can J Physiol Pharmacol. 1971 Jun;49(6):513–519. doi: 10.1139/y71-066. [DOI] [PubMed] [Google Scholar]

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

RESOURCES