Nakajima T, Nomoto K, Ohfune Y, Shiratori Y, Takemoto T, Takeuchi H, Watanabe K
Br J Pharmacol. 1985 Nov;86(3):645-54. doi: 10.1111/j.1476-5381.1985.tb08941.x.
The effects of the seven glutamic acid analogues, alpha-kainic acid, alpha-allo-kainic acid, domoic acid, erythro-L-tricholomic acid, DL-ibotenic acid, L-quisqualic acid and allo-gamma-hydroxy-L-glutamic acid were examined on six identifiable giant neurones of an African giant snail (Achatina fulica Férussac). The neurones studied were: PON (periodically oscillating neurone), d-RPLN (dorsal-right parietal large neurone), VIN (visceral intermittently firing neurone), RAPN (right anterior pallial neurone), FAN (frequently autoactive neurone) and v-RCDN (ventral-right cerebral distinct neurone). Of these, d-RPLN and RAPN were excited by the two isomers (erythro- and threo-) of beta-hydroxy-L-glutamic acid (L-BHGA), whereas PON, VIN, FAN and v-RCDN were inhibited. L-Glutamic acid (L-Glu) had virtually no effect on these neurones. alpha-Kainic acid and domoic acid showed marked excitatory effects, similar to those of L-BHGA, on d-RPLN and RAPN. Their effective potency quotients (EPQs), relative to the more effective isomer of L-BHGA were: 0.3 for both substances on d-RPLN, and 1 for alpha-kainic acid and 3-1 for domoic acid on RAPN. alpha-Kainic acid also had excitatory effects on FAN and v-RCDN (EPQ for both: 0.3), which were inhibited by L-BHGA but excited by gamma-aminobutyric acid (GABA). Erythro-L-tricholomic acid showed marked effects, similar to those of L-BHGA, on VIN (EPQ: 0.3) and RAPN (EPQ: 3-1), but produced weaker effects on PON and d-RPLN (EPQ: 0.1). DL-Ibotenic acid produced marked effects, similar to those of L-BHGA, on PON, VIN (EPQ for both: 1) and RAPN (EPQ: 1-0.3), but had weak effects on d-RPLN (EPQ: less than 0.1) and FAN (EPQ: 0.1). It had excitatory effects on v-RCDN (EPQ: 0.1). This neurone was inhibited by L-BHGA but excited by GABA. L-Quisqualic acid showed the same effects as L-BHGA on all of the neurones examined (EPQ range 30-0.1). It was the most potent of the compounds tested on RAPN (EPQ: 30-10), FAN (EPQ: 30) and v-RCDN (EPQ: 3). alpha-Allo-kainic acid and allo-gamma-hydroxy-L-glutamic acid had no obvious effect on any of the neurones examined. As described above, the responses of the neurones examined to these substances varied widely. However, L-quisqualic acid generally had effects on the neurones similar to those of L-BHGA; the L-BHGA-excited neurones were also excited by alpha-kainic acid and domoic acid.
研究了七种谷氨酸类似物,即α- kainic酸、α-别- kainic酸、软骨藻酸、赤藓糖型-L-曲古抑菌酸、DL-鹅膏蕈氨酸、L-喹啉酸和别-γ-羟基-L-谷氨酸对非洲大蜗牛(Achatina fulica Férussac)六种可识别的巨型神经元的作用。所研究的神经元有:PON(周期性振荡神经元)、d-RPLN(背侧-右侧顶叶大神经元)、VIN(内脏间歇性放电神经元)、RAPN(右前鳃神经元)、FAN(频繁自发放电神经元)和v-RCDN(腹侧-右侧脑区分明神经元)。其中,d-RPLN和RAPN被β-羟基-L-谷氨酸(L-BHGA)的两种异构体(赤藓糖型和苏阿糖型)兴奋,而PON、VIN、FAN和v-RCDN被抑制。L-谷氨酸(L-Glu)对这些神经元几乎没有影响。α- kainic酸和软骨藻酸对d-RPLN和RAPN表现出明显的兴奋作用,类似于L-BHGA的作用。它们相对于L-BHGA更有效的异构体的有效效价商(EPQ)为:两种物质对d-RPLN均为0.3,对RAPN,α- kainic酸为1,软骨藻酸为3-1。α- kainic酸对FAN和v-RCDN也有兴奋作用(两者的EPQ均为0.3),它们被L-BHGA抑制,但被γ-氨基丁酸(GABA)兴奋。赤藓糖型-L-曲古抑菌酸对VIN(EPQ:0.3)和RAPN(EPQ:3-1)表现出明显的作用,类似于L-BHGA的作用,但对PON和d-RPLN的作用较弱(EPQ:0.1)。DL-鹅膏蕈氨酸对PON、VIN(两者的EPQ均为1)和RAPN(EPQ:1-0.3)表现出明显的作用,类似于L-BHGA的作用,但对d-RPLN(EPQ:小于0.1)和FAN(EPQ:0.1)作用较弱。它对v-RCDN有兴奋作用(EPQ:0.1)。该神经元被L-BHGA抑制,但被GABA兴奋。L-喹啉酸在所检查的所有神经元上表现出与L-BHGA相同的作用(EPQ范围为30-0.1)。它是在所测试的化合物中对RAPN(EPQ:30-10)、FAN(EPQ:30)和v-RCDN(EPQ:3)作用最强的。α-别- kainic酸和别-γ-羟基-L-谷氨酸对所检查的任何神经元均无明显作用。如上所述,所检查的神经元对这些物质的反应差异很大。然而,L-喹啉酸对神经元的作用通常与L-BHGA相似;被L-BHGA兴奋的神经元也被α- kainic酸和软骨藻酸兴奋。