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Journal of Neuroscience, Vol 2, 966-971, Copyright © 1982 by Society for Neuroscience

ARTICLE

A comparative study of avermectin B1a and other modulators of the gamma- aminobutyric acid receptor . chloride ion channel complex

SS Pong, R DeHaven and CC Wang

The interactions of the anthelmintic agent avermectin B1a, the anticonvulsant pentobarbital, and the anxiolytic tracazolate with the gamma-aminobutyric acid (GABA) receptor . chloride ion channel complex in rat brain membrane were studied. The results indicated that they all potentiated ligand binding to the GABA and benzodiazepine receptors. The stimulatory effects of avermectin B1a and pentobarbital, but not tracazolate, on GABA receptor binding were inhibited by picrotoxin. The effect of avermectin B1a was not additive with those of tracazolate and pentobarbital. On the other hand, the stimulatory effect of GABA on benzodiazepine binding was additive with those of avermectin B1a and pentobarbital, but tracazolate and pentobarbital inhibited the effect of avermectin B1a. In the receptor heat inactivation experiments, avermectin B1a and clonazepam protected GABA receptors, whereas avermectin B1a and GABA protected benzodiazepine receptors. Tracazolate, pentobarbital, and picrotoxin did not protect either receptor. These findings suggest that the recognition sites for the benzodiazepines, avermectin B1a, pentobarbital, and picrotoxin are coupled allosterically to the GABA receptor . chloride ion channel complex in different ways. The binding sites for avermectin B1a may be partially shared by picrotoxin, pentobarbital, and tracazolate.

This article has been cited by other articles:

				J. Huang and J. E. Casida Avermectin B1a Binds to High- and Low-Affinity Sites with Dual Effects on the gamma -Aminobutyric Acid-Gated Chloride Channel of Cultured Cerebellar Granule Neurons J. Pharmacol. Exp. Ther., April 1, 1997; 281(1): 261 - 266. [Abstract] [Full Text]

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