Actions of avermectin B1a on the gamma-aminobutyric acidA receptor and chloride channels in rat brain.
Actions of avermectin B1a on the gamma-aminobutyric acidA receptor and chloride channels in rat brain.
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阿维菌素 B1a 对大鼠脑中 γ-氨基丁酸 A 受体和氯离子通道的作用。
DOI：
10.1002/jbt.2570010108
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发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Eldefrawi,ME
中科院分区：
文献类型：
--
作者：
Abalis,IM;Eldefrawi,AT;Eldefrawi,ME
用放射性配体结合和示踪离子流分析法研究了阿维菌素B1 a（AVM）与大鼠脑γ-氨基丁酸（GABA）受体的相互作用。阿维菌素可增强[3 H]氟硝西泮的结合，并抑制[3 H]蝇蕈醇和[35 S]叔丁基双环硫代磷酸酯与GABAA受体的结合。AVM对蝇蕈醇结合的抑制表明竞争性置换。研究了两种36氯离子（Cl）助熔剂。AVM可增强36 Cl从预载微囊的流出，并可被Cl-通道阻断剂4，4 ′-二异硫氰基-2，2 ′-二苯乙烯二磺酸（DIDS）高度抑制。然而，它不是由GABA增强，也不是对惊厥剂印防己毒素或荷包牡丹碱敏感。另一方面，大鼠脑不同微囊制备物中的36 Cl-内流测量对GABA和其他GABA能药物非常敏感。阿维菌素以剂量依赖的方式诱导~（36）Cl内流进入这些微囊，但仅为GABA诱导的最大内流的35%。AVM诱导的36 Cl内流被荷包牡丹碱完全阻断。这表明AVM通过与GABA识别位点结合并作为部分受体激动剂打开GABAA-受体Cl通道，还打开对GABA完全不敏感但对DIDS非常敏感的电压依赖性Cl通道。
The interaction of avermectin B1a(AVM) with the γ‐aminobutyric acid (GABA) receptor of rat brain was studied using radioactive ligand binding and tracer ion flux assays. Avermectin potentiated the binding of [3H]flunitrazepam and inhibited the binding of both [3H]muscimol and [35S]t‐butylbicyclo‐phosphorothionate to the GABAAreceptor. Inhibition of muscimol binding by AVM suggested competitive displacement. Two kinds of36chloride (Cl) flux were studied. The36Cl efflux from preloaded microsacs was potentiated by AVM and was highly inhibited by the Cl‐channel blocker 4,4′‐diisothiocyano‐2,2′‐stilbenedisulfonic acid (DIDS). However, it was not potentiated by GABA nor was it sensitive to the convulsants picrotoxin or bicuculline. On the other hand,36Cl‐influx measurement in a different microsac preparation of rat brain was very sensitive to GABA and other GABA‐ergic drugs. Avermectin induced36Cl influx into these microsacs in a dose–dependent manner, but to only 35% of the maximal influx induced by GABA. The AVM‐induced36Cl influx was totally blocked by bicuculline. It is suggested that AVM opens the GABAA‐receptor Cl channel by binding to the GABA recognition site and acting as a partial receptor agonist, and also opens a voltage–dependent Cl channel which is totally insensitive to GABA but is very sensitive to DIDS.