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. 1986 Apr;87(4):677–684. doi: 10.1111/j.1476-5381.1986.tb14585.x

Quantitative evaluation of the potencies of GABA-receptor agonists and antagonists using the rat hippocampal slice preparation.

J A Kemp, G R Marshall, G N Woodruff
PMCID: PMC1916810  PMID: 3011168

Abstract

CA1 population spikes recorded in the rat hippocampal slice were used to assess quantitatively the potencies of GABA-receptor agonists and antagonists on mammalian CNS neurones. Apart from GABA itself, GABA A-receptor agonists inhibited the CA1 population spikes with potencies that correlated closely (r = 0.96) with their ability to displace [3H]-GABA from GABAA-binding sites. The low potency of GABA in this preparation was attributed to the action of uptake processes as the GABA uptake inhibitor, cis-4-hydroxynipecotic acid (2 X 10(-4) M), produced an approximate 6 fold increase in the potency of GABA whilst having no effect on the potency of 4,5,6,7-tetrahydroisoxazolo [5,4-c] pyridin-3-ol (THIP), a GABAA-receptor agonist which is not a substrate for the GABA uptake system. The inhibitory effects of the selective GABAA-receptor agonists isoguvacine and muscimol were antagonized by bicuculline methochloride, which shifted the dose-response curves to the right in a parallel manner. The Schild plots for bicuculline methochloride against isoguvacine and muscimol had slopes of 1 and gave pA2 values of 6.24 and 6.10, respectively. Picrotoxin also antagonized the inhibitory effects of isoguvacine and produced parallel shifts to the right of the dose-response curve. However, the Schild plot for picrotoxin had a slope significantly less than unity (0.82) and gave a pA2 value of 6.89. The novel GABAA-receptor antagonist, pitrazepin, antagonized the inhibitory effects of isoguvacine in an apparently competitive manner. The Schild plot had a slope of 1 and gave a pA2 of 6.69.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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