ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: The ability of γ-aminobutyric acid (GABA) and glycine (Gly) to modulate each other's release was studied in synaptosomes from rat spinal cord, cerebellum, cerebral cortex, or hippocampus, prelabeled with [3H]GABA or [3H]-Gly and exposed in superfusion to Gly or to GABA, respectively. GABA increased the spontaneous outflow of [3H]Gly (EC50, 20.8 μM) from spinal cord synaptosomes. Neither muscimol nor (-)-baclofen, up to 300 μM, mimicked the effect of GABA, which was not antagonized by either bicuculline or picrotoxin. However, the effect of GABA was counteracted by the GABA uptake inhibitors nipecotic acid and N-(4,4-diphenyl-3-butenyl)nipecotic acid. Moreover, the GABA-induced [3H]Gly release was Na+ dependent and disappeared when the medium contained 23 mM Na+. The effect of GABA was Ca2+ independent and tetrodotoxin insensitive. Conversely, Gly enhanced the outflow of [3H]-GABA from rat spinal cord synaptosomes (EC50, 100.9 μM). This effect was insensitive to both strychnine and 7-chlorokynurenic acid, antagonists at Gly receptors, but it was strongly Na+ dependent. Also, the Gly-evoked [3H]-GABA release was Ca2+ independent and tetrodotoxin insensitive. GABA increased the outflow of [3H]Gly (EC50, 11.1 μM) from cerebellar synaptosomes; the effect was not mimicked by either muscimol or (—)-baclofen nor was it prevented by bicuculline or picrotoxin. The GABA effect was, however, blocked by GABA uptake inhibitors and was Na+ dependent. Gly increased [3H]GABA release from cerebellar synaptosomes (EC50, 110.7 μM) in a strychnine- and 7-chlorokynurenic acid-insensitive manner. This effect was Na+ dependent. The effects of GABA on [3H]Gly release seen in spinal cord and cerebellum could be reproduced also with cerebrocortical synaptosomes. However, in cortex, the effect of Gly on [3H]GABA release was much lower than in spinal cord or cerebellum, although it was partly Na+ dependent. No changes of [3H]Gly release were observed in hippocampal synaptosomes exposed to GABA. It is suggested that transporters specific for GABA or Gly are colocalized on the same nerve terminal in rat spinal cord, cerebellum, and cerebral cortex, but not in hippocampus. Moreover, GABA uptake modulates Gly release and, at least in spinal cord and cerebellum, Gly uptake modulates GABA release. These conclusions are compatible with the reported coexistence of GABA and Gly in spinal and cerebellar neurons.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1992.tb08464.x
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