Yongsiri A, Funase K, Takeuchi H, Shimamoto K, Ohfune Y
Department of Physiology, Gifu University School of Medicine, Japan.
Eur J Pharmacol. 1988 Oct 18;155(3):239-45. doi: 10.1016/0014-2999(88)90509-2.
The present study aimed to elucidate the pharmacological features of GABA receptors on identifiable neurones of Achatina fulica Férussac by testing the effects of GABA analogues, muscimol, (+/-)-baclofen, (-)-beta-hydroxy GABA and those conformationally fixed in either the extended or folded form of carbon chain, such as trans- and cis-isomers of (+/-)-2-(aminomethyl)cyclopropane-1-carboxylic acid [+/-)-cyclo-GABA-extended and (+/-)-cyclo-GABA-folded) and trans-4-amino-crotonic acid (GABA-extended). The giant neurones used were TAN, d-LPeLN, v-VNAN, v-LCDN and RPeNLN. The minimum effective concentrations (MEC) of these compounds to produce hyper- or depolarization of the membrane potentials of the neurones were determined, and the effective potency quotient (EPQ) of each compound vis-à-vis that of GABA was calculated for each neurone. The GABA receptors in these neurones were classified into the muscimol I, muscimol II and baclofen types. The muscimol I (TAN and d-LPeLN) and muscimol II (v-VNAN and v-LCDN) receptors were respectively hyperpolarized and depolarized by GABA and muscimol but were insensitive to (+/-)-baclofen. These muscimol receptors are inferred to accept GABA in an extended form of its carbon chain, since muscimol, conformationally fixed in this form from C-1 to C-4, was quite effective. Muscimol was more potent on the muscimol II receptors (MEC: 3 X 10(-7)-3 X 10(-6) M; EPQ: 30-10) than on the muscimol I type (MEC: 3 X 10(-5)-10(-4) M; EPQ: 1-0.3).(ABSTRACT TRUNCATED AT 250 WORDS)
本研究旨在通过测试γ-氨基丁酸(GABA)类似物、蝇蕈醇、(±)-巴氯芬、(-)-β-羟基GABA以及那些碳链呈伸展或折叠形式的构象固定类似物,如(±)-2-(氨甲基)环丙烷-1-羧酸的反式和顺式异构体[(±)-环-GABA-伸展型和(±)-环-GABA-折叠型]以及反式-4-氨基巴豆酸(GABA-伸展型)对非洲大蜗牛可识别神经元上GABA受体的药理学特性。所使用的巨型神经元为TAN、d-LPeLN、v-VNAN、v-LCDN和RPeNLN。测定了这些化合物使神经元膜电位产生超极化或去极化的最小有效浓度(MEC),并为每个神经元计算了每种化合物相对于GABA的有效效价商(EPQ)。这些神经元中的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(TAN和d-LPeLN)和蝇蕈醇II型(v-VNAN和v-LCDN)受体分别被GABA和蝇蕈醇超极化和去极化,但对(±)-巴氯芬不敏感。由于从C-1到C-4呈这种构象固定形式的蝇蕈醇非常有效,因此推断这些蝇蕈醇受体以碳链的伸展形式接受GABA。蝇蕈醇对蝇蕈醇II型受体(MEC:3×10⁻⁷ - 3×10⁻⁶ M;EPQ:30 - 10)的效力比对蝇蕈醇I型(MEC:3×10⁻⁵ - 10⁻⁴ M;EPQ:1 - 0.3)更强。(摘要截断于250字)