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  • Title: Avermectin modulation of GABA binding to membranes of rat brain, brine shrimp and a fungus, Mucor miehei.
    Author: Calcott PH, Fatig RO.
    Journal: J Antibiot (Tokyo); 1984 Jul; 37(7):797-801. PubMed ID: 6088460.
    Abstract:
    High affinity [3H]GABA (gamma-aminobutyric acid) binding sensitive to muscimol and bicuculline was detected in membranes derived from rat brain and brine shrimp. Avermectin stimulated this GABA binding with maximum stimulation seen in these membranes at 400 and 40-80 ng/ml, respectively. This avermectin stimulation of GABA binding was Cl--dependent, bicuculline and picrotoxin-sensitive and was associated with an increase in Bm but not Kd of the systems. The membranes from Mucor miehei also exhibited high affinity [3H]GABA binding that was insensitive to classical neuronal GABA receptor agonists/antagonists and other agents. This novel GABA receptor was sensitive to Na+ and extremely sensitive to low levels of avermectin (apparent Ki 20-40 ng/ml). This inhibition of GABA binding by avermectin was associated with a decrease in affinity (increase in Kd) and an increase in concentration of receptors (Bm). It is possible that these GABA receptors might play crucial roles in control of cell metabolism and that avermectin can prevent growth of this organism via interference in the receptor activity.
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