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A novel type of GABA receptor in rat spinal cord?

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Summary

The depolarization-evoked release of γ-aminobutyric acid (GABA) and its possible modulation mediated by autoreceptors were studied in nerve endings isolated from rat spinal cord and prelabeled with the radioactive aminoacid. In the presence of the GABA uptake inhibitor SK&F 89976A [N-(4,4-diphenyl-3-butenyl)-nipecotic acid], used to minimize carrier-mediated homoexchange, exogenous GABA (1–10 µmol/l) decreased in a concentration-dependent way the release of3H-GABA evoked by 15 mmol/l KCl. The GABAA receptor agonist muscimol (10–100 µmol/l) did not affect the K+(15 mmol/l)-evoked3H-GABA release. Similarly ineffective was the GABAB receptor agonist (−)-baclofen (3–100 µmol/l). The effect of GABA was not counteracted by the GABAA receptor antagonists bicuculline,picrotoxinorSR95531 [2-(3′-carbethoxy-2′-propenyl)-3-amino-6-paramethoxy-phenyl-pyridazinium bromide]. In a set of experiments performed in parallel with spinal cord or cerebral cortex synaptosomes depolarized with 9 mmol/l KCI it was found that: (a) GABA (1–10 µmol/l) decreased in a concentration-dependent way the release of3H-GABA in both brain regions and its effects were practically doubled when compared with those in synaptosomes depolarized with 15 mmol/l KCI; - (b) muscimol (1–100 µmol/l) was ineffective both in spinal cord and in cerebral cortex; - (c) (−)-baclofen (1-100 µmol/l) concentration-dependently inhibited3H-GABA release in cerebral cortex synaptosomes but was almost inactive in the spinal cord; the (+)-enantiomer of baclofen (100 µmol/l) did not affect significantly the release of3H-GABA; - (d) the GABAB receptor antagonist phaclofen [3-amino-2-(4chlorophenyl)-propyl phosphonic acid] antagonized the effect of GABA in cerebral cortex but not in spinal cord synaptosomes. It is concluded that the release of GABA in rat spinal cord may be modulated by an autoreceptor which does not belong to the known GABA receptor subtypes.

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Raiteri, M., Pellegrini, G., Cantoni, C. et al. A novel type of GABA receptor in rat spinal cord?. Naunyn-Schmiedeberg's Arch. Pharmacol. 340, 666–670 (1989). https://doi.org/10.1007/BF00717742

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