Effects of GABA analogues of restricted conformation on GABA transport in astrocytes and brain cortex slices and on GABA receptor binding.
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Biomedical subjects
Publications and source records attributed to P Krogsgaard-Larsen.
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Contralateral turning behaviour following unilateral intranigral injection of a large series of GABA analogues was investigated. The results indicated that the turning behaviour was induced stereospecifically and was selectively antagonized by the GABA antagonist bicuculline methochloride. The comparative potencies of a series of GABA agonists related to muscimol in general corresponded well to the affinity for 3H-GABA receptor sites and to the depressant action on single neurons using microelectrophoretic administration. However, the GABA agonists trans-aminocrotonic acid and 3-aminopropanesulphonic acid were much weaker than expected from in vitro studies. The GABA-uptake inhibitors nipecotic acid and guvacine showed only weak and short-lasting effects. The GABA-transaminase inhibitor gamma-acetylenic GABA showed delayed effects compared with the agonists which acted immediately. It is proposed that this behavioural effect may be a sensitive and quantitative method for evaluation of GABA agonists in vivo.
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Intracellular recordings have been made from GABA sensitive neurones in the central nervous system of Limulus and Helix. The following conformationally restricted analogues of GABA all possessed GABA-like activity on Limulus neurones and Helix excitatory GABA receptors: muscimol, thiomuscimol, THIP, isoguvacine and piperidine-4- carboxylic acid. It is suggested that GABA interacts with these receptors in a partially extended and almost planar conformation.
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