avermectin-b(1)a and picrotoxinin

The stimulatory effects of secobarbital and pregnanolone on GABA receptor binding could be distinguished by their sensitivity to blockade by phenobarbital, avermectin B1a and picrotoxinin. Phenobarbital (1 mM) and avermectin (10(-9)-10(-6) M) inhibited the stimulation of [3H]muscimol binding to pig brain membranes caused by secobarbital but not that caused by pregnanolone. In contrast, enhancement of [3H]muscimol binding by pregnanolone showed a greater sensitivity to the inhibitory effects of picrotoxinin. These results, together with data demonstrating an additivity of barbiturate- and steroid-induced effects, indicate that these two classes of modulators may interact with the GABAA receptor through different sites.

Topics: Animals; Anthelmintics; Cerebral Cortex; In Vitro Techniques; Ivermectin; Muscimol; Phenobarbital; Picrotoxin; Pregnanes; Pregnanolone; Radioligand Assay; Receptors, GABA-A; Secobarbital; Sesterterpenes; Swine; Synaptic Membranes

Avermectin B1a concentrations corresponding to the KD value of a specific high affinity binding site for [3H]avermectin B1a are sufficient to stimulate the specific high affinity binding of [3H]flunitrazepam to its receptors. This stimulation of [3H]flunitrazepam binding by low concentrations of avermectin B1a was enhanced by chloride ions and picrotoxinin and reduced by the GABA agonists THIP and PSA. The similar modulation by chloride ions, GABA agonists and picrotoxinin and the resistance against washing of membranes of avermectin B1a bound to its specific high affinity binding site or to the site modulating [3H]flunitrazepam binding indicate a close association of the specific high affinity binding site for [3H]avermectin B1a with the GABA-benzodiazepine receptor complex.

Topics: Animals; Binding Sites; Binding, Competitive; Cell Membrane; Cerebellar Cortex; Chlorides; Flunitrazepam; In Vitro Techniques; Ivermectin; Lactones; Picrotoxin; Rats; Receptors, Cell Surface; Receptors, GABA-A; Sesterterpenes; Temperature