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非洲大蜗牛巨型神经元对假定氨基酸神经递质的敏感性。

Sensitivities of Achatina giant neurones to putative amino acid neurotransmitters.

作者信息

Takeuchi H

机构信息

Department of Physiology, Gifu University School of Medicine, Japan.

出版信息

Comp Biochem Physiol C Comp Pharmacol Toxicol. 1992 Sep;103(1):1-12. doi: 10.1016/0742-8413(92)90219-w.

Abstract
  1. GABA receptors in Achatina identifiable giant neurones were classified into the muscimol I, muscimol II and baclofen types. Muscimol I and II type GABA receptors were sensitive to GABA and muscimol but insensitive to baclofen, whereas baclofen type receptors were sensitive to GABA and baclofen but insensitive to muscimol. Muscimol I and baclofen types were associated with the inhibition caused by GABA, while muscimol II type with the GABA excitation. 2. GABA, muscimol and TACA produced a transient outward current (Iout) with an increase in membrane conductance (g) of an Achatina neurone, TAN, having the muscimol I type GABA receptors. Their relative potency values (RPV) at GABA ED50 (approximately 10(-4) M) were: GABA:muscimol:TACA = 1:0.6:0.3. The GABA effects were potentiated by pentobarbitone, antagonized competitively by pitrazepin and non-competitively by picrotoxin and diazepam, and unaffected by bicuculline. The ionic mechanism of effects of GABA and its two analogues was the increase in membrane Cl- conductance (gCl). 3. GABA and (+/-)-baclofen produced a slow Iout with a g increase of another Achatina neurone, RPeNLN, having the baclofen type GABA receptors. The two compounds were almost equipotent (ED50: approximately 3 x 10(-4) M). The ionic mechanism of their effects was the increase in gk. The two compounds hardly affected the voltage-gated and slowly inactivating calcium current. Iout produced by GABA and (+/-)-baclofen were reduced by TEA, but unaffected by 4-AP, bicuculline, pitrazepin and picrotoxin. 4. Beta-hydroxy-L-glutamic acid (L-BHGA) showed the marked effects on the Achatina giant neurones; the two neurones were excited by the compound, whereas the three inhibited. D-BHGA, L-Glu, D-Glu and NMDA were less effective than L-BHGA or almost ineffective. Erythro-L-BHGA was more or less effective than threo-L-BHGA according to the neurones tested. 5. alpha-Kainic acid and domoic acid excited the two neurones, which were excited by L-BHGA. L-Quisqualic acid showed the similar effects to L-BHGA, which were mostly much stronger than L-BHGA. Erythro-L-tricholomic acid and DL-ibotenic acid showed the effects similar to L-BHGA selectively on some neurones. 6. It was pointed out that the pharmacological features of GABA on the Achatina neurones are simpler than those of L-BHGA, due to the simpler structure of the former compound having less binding sites than the latter.
摘要
  1. 可在玛瑙螺可识别的巨型神经元中,γ-氨基丁酸(GABA)受体被分为蝇蕈醇I型、蝇蕈醇II型和巴氯芬型。蝇蕈醇I型和II型GABA受体对GABA和蝇蕈醇敏感,但对巴氯芬不敏感,而巴氯芬型受体对GABA和巴氯芬敏感,但对蝇蕈醇不敏感。蝇蕈醇I型和巴氯芬型受体与GABA引起的抑制作用有关,而蝇蕈醇II型与GABA兴奋作用有关。2. GABA、蝇蕈醇和TACA在具有蝇蕈醇I型GABA受体的玛瑙螺神经元(TAN)中产生了瞬时外向电流(Iout),同时膜电导(g)增加。它们在GABA半数有效浓度(ED50,约10⁻⁴ M)时的相对效价(RPV)为:GABA:蝇蕈醇:TACA = 1:0.6:0.3。GABA的作用被戊巴比妥增强,被匹拉唑平竞争性拮抗,被印防己毒素和地西泮非竞争性拮抗,且不受荷包牡丹碱影响。GABA及其两种类似物作用的离子机制是膜氯离子电导(gCl)增加。3. GABA和(±)-巴氯芬在具有巴氯芬型GABA受体的另一个玛瑙螺神经元(RPeNLN)中产生了缓慢的Iout,同时g增加。这两种化合物几乎等效(ED50:约3×10⁻⁴ M)。它们作用的离子机制是gk增加。这两种化合物几乎不影响电压门控和缓慢失活的钙电流。GABA和(±)-巴氯芬产生的Iout被四乙铵(TEA)降低,但不受4-氨基吡啶(4-AP)、荷包牡丹碱、匹拉唑平和印防己毒素影响。4. β-羟基-L-谷氨酸(L-BHGA)对玛瑙螺巨型神经元有显著作用;两个神经元被该化合物兴奋,而另外三个被抑制。D-BHGA、L-谷氨酸、D-谷氨酸和N-甲基-D-天冬氨酸(NMDA)比L-BHGA效果差或几乎无效。根据所测试的神经元,赤藓糖型-L-BHGA比苏阿糖型-L-BHGA或多或少更有效。5. α- kainic酸和软骨藻酸兴奋了两个被L-BHGA兴奋的神经元。L-喹啉酸表现出与L-BHGA相似的作用,大多比L-BHGA强得多。赤藓糖型-L-口蘑氨酸和DL-鹅膏蕈氨酸选择性地对一些神经元表现出与L-BHGA相似的作用。

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