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秀丽隐杆线虫中γ-氨基丁酸及其结合位点的鉴定。

Identification of gamma-aminobutyric acid and its binding sites in Caenorhabditis elegans.

作者信息

Schaeffer J M, Bergstrom A R

机构信息

Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey 07065.

出版信息

Life Sci. 1988;43(21):1701-6. doi: 10.1016/0024-3205(88)90481-x.

DOI:10.1016/0024-3205(88)90481-x
PMID:2848169
Abstract

Gamma-aminobutyric acid (GABA), glutamate decarboxylase and GABA-transaminase were identified in the nematode Caenorhabditis elegans. The concentration of GABA in C. elegans (0.14 micrograms/mg protein) is approximately 10-fold lower than the concentration of GABA in rat brain. Glutamate decarboxylase and GABA-transaminase, the GABA anabolic and catabolic enzymes, are also present in C. elegans. Crude membrane fractions were prepared from C. elegans and used to study specific [3H] GABA binding sites. GABA binds to C. elegans membranes with high affinity (37 nM) and low capacity (Bmax = 2.25 pmol/mg protein). Muscimol is a competitive inhibitor of specific GABA binding with a KI value of 120 nM. None of the other GABA agonists or antagonists inhibited greater than 40% of the specific GABA binding at concentrations up to 10(-4)M. Thirteen spider venoms were examined as possible GABA agonists or antagonists, the venom from Calilena agelenidae inhibits specific GABA binding with a KI value of 6 nl/ml. These results suggest that GABA has a physiological role as a neurotransmitter in C. elegans.

摘要

在秀丽隐杆线虫中鉴定出了γ-氨基丁酸(GABA)、谷氨酸脱羧酶和GABA转氨酶。秀丽隐杆线虫中GABA的浓度(0.14微克/毫克蛋白质)比大鼠脑中GABA的浓度低约10倍。GABA合成和分解代谢酶谷氨酸脱羧酶和GABA转氨酶也存在于秀丽隐杆线虫中。从秀丽隐杆线虫制备粗膜组分,用于研究特异性[3H]GABA结合位点。GABA以高亲和力(37 nM)和低容量(Bmax = 2.25 pmol/毫克蛋白质)与秀丽隐杆线虫膜结合。蝇蕈醇是特异性GABA结合的竞争性抑制剂,KI值为120 nM。在浓度高达10^(-4)M时,其他GABA激动剂或拮抗剂均未抑制超过40%的特异性GABA结合。检测了13种蜘蛛毒液作为可能的GABA激动剂或拮抗剂,阿氏姬蛛的毒液以6 nl/ml的KI值抑制特异性GABA结合。这些结果表明GABA在秀丽隐杆线虫中作为神经递质具有生理作用。

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