Neurochemical Research

, Volume 15, Issue 9, pp 905–910 | Cite as

Effects of GABA antagonists, SR 95531 and bicuculline, on GABAA receptor-regulated chloride flux in rat cortical synaptoneurosomes

  • Sue Yu
  • I. K. Ho
Original Articles
Accepted:

Abstract

Synaptoneurosomes isolated from cerebral cortices of male Sprague-Dawley rats were used for studying GABAA receptor-regulated chloride influx. The in vitro effects of GABA antagonists, SR 95531 (a pyridazinyl GABA derivative) and bicuculline, on pentobarbital-stimulated, muscimol-stimulated or flunitrazepam-enhanced, muscimol-stimulated chloride uptake were studied. The chloride uptake was determined at 30°C, for 5 sec. Pentobarbital and muscimol produced a maximal stimulation of chloride uptake in cortical synaptoneurosomes at 500 μM and 50μM, respectively. SR 95531 as well as bicuculline had no effect on the basal uptake of chloride. Whereas, SR 95531 (0.3–30 μM) and bicuculline (0.1–100 μM), when added 5 min before muscimol (50 μM), produced a significant concentration-dependent inhibition of muscimol (50 μM)-stimulated chloride uptake (IC50s of 0.89±0.11 μM and 13.45±2.10μM, respectively). In studies of the inhibitory effects of SR 95531 and bicuculline on pentobarbital (500 μM)-stimulated chloride uptake, the IC50s were 0.81±0.12 μM and 3.86±1.14 μM, respectively. SR 95531 exhibited a more potent inhibitory effect than bicuculline on flunitrazepam-enhanced, muscimol-stimulated chloride uptake. The results revealed that SR 95531 has a more potent antagonistic effect than bicuculline on GABAA-regulated chloride flux.

Key Words

SR 95531 bicuculline chloride uptake GABAA receptor 
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Copyright information

© Plenum Publishing Corporation 1990

Authors and Affiliations

  • Sue Yu
    • 1
  • I. K. Ho
    • 1
  1. 1.Department of Pharmacology and ToxicologyUniversity of Mississippi Medical CenterJackson

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