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In Vitro Modulation by Avermectin B 1 a of the GABA/Benzodiazepine Receptor Complex of Rat Cerebellum
Author(s) -
Supavilai Porntip,
Karobath Manfred
Publication year - 1981
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1981.tb01664.x
Subject(s) - avermectin , chemistry , bicuculline , gabaa receptor , receptor , binding site , pharmacology , benzodiazepine , agonist , biochemistry , flunitrazepam , biophysics , stereochemistry , biology , anatomy
Avermectin B 1 a, a macrocyclic lactone anthelmintic agent, causes a concentration‐dependent increase of [ 3 H]flunitrazepam binding to membranes from rat cerebellum by increasing the affinity and the number of binding sites. This effect appears to be independent of the concentration of chloride ions. The effects of avermectin B 1 a occur with high affinity (EC 50 = 70 nM), and they persist after washing of the membranes with drug‐free buffer. Pretreatment of the membranes with Triton X‐100 completely abolishes the action of avermectin B 1 a. GABA and the GABA‐mimetic compounds piperidine‐4‐sulfonic acid and THIP diminish the effects of avermectin B 1 a on benzodiazepine receptor binding in a bicuculline‐methiodide‐sensitive mode. In addition, the stimulation of [ 3 H]flunitrazepam binding by avermectin B 1 a is decreased by the pyrazolopyridines etazolate and cartazolate. These observations suggest that avermectin B 1 a stimulates benzodiazepine receptor binding by acting on a modulatory site which 1s independent of the GABA recognition site and of the drug receptor for the pyrazolopyridines, but which is in functional interaction with these sites.