gamma-Aminobutyric acid agonists: an in vitro comparison between depression of spinal synaptic activity and depolarization of spinal root fibres in the rat.
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).
D000818:Animals; D001921:Brain / Q000378:metabolism; D066298:In Vitro Techniques; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013126:Spinal Nerve Roots / Q000187:drug effects* / Q000502:physiology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter; D005680:gamma-Aminobutyric Acid