Witt M R, Nielsen M
Biochemical Department, St. Hans Hospital, Roskilde, Denmark.
J Neurochem. 1994 Apr;62(4):1432-9. doi: 10.1046/j.1471-4159.1994.62041432.x.
We have investigated the effect of unsaturated free fatty acids (FFAs) on the brain GABA/benzodiazepine receptor chloride channel complex from mammalian, avian, amphibian, and fish species in vitro. Unsaturated FFAs with a carbon chain length between 16 and 22 carbon atoms enhanced [3H]diazepam binding in rat brain membrane preparations, whereas the saturated analogues had no effect. The enhancement of [3H]diazepam binding by oleic acid was independent of the incubation temperature (0-30 degrees C) of the binding assay and not additive to the enhancement by high concentrations of Cl-. In rat brain preparations, the stimulation of [3H]diazepam binding by oleic acid (10(-4) M) was independent of the ontogenetic development. Phylogenetically, large differences were found in the effect of unsaturated FFAs on [3H]diazepam and [3H]muscimol binding: In mammals and amphibians, unsaturated FFAs enhanced both [3H]-muscimol and [3H]diazepam binding to 150-250% of control binding. In 17 fish species studied, oleic acid (10(-4) M) stimulation of [3H]diazepam binding was weak (11 species), absent (four species), or reversed to inhibition (two species), whereas stimulation of [3H]muscimol binding was of the same magnitude as in mammals and amphibians. In 10 bird species studied, only weak enhancement of [3H]muscimol binding (110-130% of control) by oleic acid (10(-4) M) was found, whereas [3H]diazepam binding enhancement was similar to values in mammal species. Radiation inactivation of the receptor complex in situ from frozen rat cortex showed that the functional target size for oleic acid to stimulate [3H]flunitrazepam binding has a molecular mass of approximately 200,000 daltons.(ABSTRACT TRUNCATED AT 250 WORDS)
我们在体外研究了不饱和游离脂肪酸（FFA）对哺乳动物、鸟类、两栖动物和鱼类的脑γ-氨基丁酸/苯二氮䓬受体氯化物通道复合物的影响。碳链长度在16至22个碳原子之间的不饱和FFA增强了大鼠脑膜制剂中[³H]地西泮的结合，而饱和类似物则无此作用。油酸对[³H]地西泮结合的增强作用与结合试验的孵育温度（0至30摄氏度）无关，且与高浓度氯离子的增强作用无相加性。在大鼠脑制剂中，油酸（10⁻⁴ M）对[³H]地西泮结合的刺激作用与个体发育无关。从系统发育角度来看，不饱和FFA对[³H]地西泮和[³H]蝇蕈醇结合的影响存在很大差异：在哺乳动物和两栖动物中，不饱和FFA使[³H] - 蝇蕈醇和[³H]地西泮的结合增强至对照结合的150 - 250%。在所研究的17种鱼类中，油酸（10⁻⁴ M）对[³H]地西泮结合的刺激作用较弱（11种）、不存在（4种）或逆转至抑制（2种），而对[³H]蝇蕈醇结合的刺激作用与哺乳动物和两栖动物中的程度相同。在所研究的10种鸟类中，仅发现油酸（10⁻⁴ M）对[³H]蝇蕈醇结合有微弱增强（为对照的110 - 130%），而[³H]地西泮结合增强与哺乳动物中的值相似。对冷冻大鼠皮层原位受体复合物进行辐射失活表明，油酸刺激[³H]氟硝西泮结合的功能靶点大小的分子量约为200,000道尔顿。（摘要截于250字）
