gamma-Aminobutyric acid agonists: an in vitro comparison between depression of spinal synaptic activity and depolarization of spinal root fibres in the rat

Br J Pharmacol. 1980 Dec;70(4):609-15. doi: 10.1111/j.1476-5381.1980.tb09779.x.

Abstract

1 Relative molar potencies, of a range of gamma-aminobutyrate (GABA)-related agonists, for depolarization of isolated spinal roots have been compared with their potencies for depression of spontaneous synaptic activity, recorded in ventral roots of hemisected spinal cord preparations from 3 to 9-day-old rats. Both effects were sensitive to antagonism by bicuculline. 2 The depolarizing potencies of the series were not parallelled by their depressant potencies. This disparity was shown most strongly by 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) which was 20 times stronger than GABA in depolarizing root fibres and 20 times stronger than GABA in its depressant action and by (+)-cis-3-aminocyclopentane-carboxylic acid (17 times weaker than GABA on root fibres and 42 times stronger than GABA as a depressant). 3 The effect of uptake on these relative potencies is discussed and it is concluded that fibre depolarization and depression are probably mediated by different types of bicuculline-sensitive receptor. 4 The depolarizing potencies of the agonists showed a strong correlation with previously reported data for displacement of labelled GABA from in vitro rat brain membrane preparations (correlation coefficient 0.90, P less than 0.001). However, the relative depressant potencies showed no such correlation with binding data (correlation coefficient 0.50, P less than 0.05).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • In Vitro Techniques
  • Rats
  • Receptors, Cell Surface / drug effects
  • Receptors, GABA-A
  • Receptors, Neurotransmitter / drug effects
  • Spinal Cord / drug effects*
  • Spinal Cord / physiology
  • Spinal Nerve Roots / drug effects*
  • Spinal Nerve Roots / physiology
  • Synapses / drug effects*
  • Synapses / physiology
  • gamma-Aminobutyric Acid / metabolism
  • gamma-Aminobutyric Acid / pharmacology*

Substances

  • Receptors, Cell Surface
  • Receptors, GABA-A
  • Receptors, Neurotransmitter
  • gamma-Aminobutyric Acid