Effects of picrotoxin and bicuculline on the muscimol-dependent 36C1-entry into synaptoneurosomes of the rat cerebral cortex are examined as well as desensitization of 36El-entry at muscimol concentrations of 5 and 50 rtM. At the 5 gM concentration (which is close to the muscimol IC50), picrotoxin and bicuculline inhibited C1-entry into synaptoneurosomes and decreased the desensitization. At the 50 gM concentration, muscimol completely abolishes the bicuculline effects both on C1-entry and desensitization. Inhibition of C1-entry by picrotoxin is also abolished by 50 gM muscimol, whereas the picrotoxin-induced decrease in the desensitization rate is not. It is shown that both bicuculline effects result from inhibition of the GABA receptor, but the action of picrotoxin on the desensitization of C1-entry into synaptoneurosomes is not closely related to the functional activity of the GABA receptor/C1-channel complex.Key Words: desensitization; muscimol; picrotoxin; bicuculline; synaptoneurosomes Desensitization of the GABA receptor/C1-channel complex is a process whereby the GABA-stimulated C1-conductivity is progressively decreased [3,4,6,9]. It is still unknown whether this desensitization represents a reduction in receptor sensitivity to GABA or a decrease in the conductivity of C1-channel. The difficulties encountered in seeking the correct answer to this question stem from the fact that it is not possible to study the C1-channel conductivity separately from activation of the GABA receptor. The only alternative that remains is analysis of how the desensitization is influenced by inhibitors and modulators of the GABA receptor/C1-complex with different mechanisms of action.Institute of General Pathology and Pathophysiology, Russian Academy of Medical Sciences, Moscow This study continues and extends our previously initiated investigation [1,2] to compare the effects of the competitive inhibitor of the GABA, receptor bicuculline (BC) and of the C1-channel blockers picrotoxin (PT) and pentylenetetrazole on the desensitization of the GABA receptor/C1-channel complex.
MATERIALS AND METHODSSynaptoneurosomes (SNS) were isolated using our modification [2] of a previously described procedure [7]. Randomly bred male rats (body weight 180-200 g) were decapitated, and their cerebral cortex was removed and homogenized at 0-4~ manually (5 frictions) in a glass homogenizer with a Teflon pestle in Krebs--Ringer's medium of the following composition (mM): 145 NaC1, 5 KC1, 1 MgSO4, 1 CaC1 v 10 glucose, and 10 HEPES (pH 7.4, 20~ in a ra-
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