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Sensitivities of Achatina giant neurones to putative amino acid neurotransmitters
Institution:1. Department of Psychiatry, Tel-Aviv Sourasky Medical Center & Sackler Faculty of Medicine, Tel Aviv University, Israel;2. Department of Physics of Complex Systems, Weizmann Institute of Science, Rehovot, Israel;3. Psychobiology Research Lab, Department of Neuroscience, The Ruth and Bruce Rappaport Faculty of Medicine, Technion - Israel Institute of Technology, Haifa, Israel;4. Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel;5. Sagol School for Neuroscience, Tel Aviv University, Tel Aviv, Israel;6. Shalvata Mental Health Center, Affiliated with the Sackler School of Medicine, Tel-Aviv University, Israel;1. Department of Chemistry, University of Agriculture, Faisalabad, 38000, Pakistan;2. Punjab Bio-energy Institute, University of Agriculture, Faisalabad, 38040, Pakistan;4. Jean Mayer USDA Human Nutrition Research Center on Aging, Boston, MA;5. School of Medicine, Tufts University, Boston, MA;6. Biomedical Informatics and Computational Biology, Minneapolis, MN;7. Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN;8. Bell Institute of Health and Nutrition, General Mills, Minneapolis, MN;1. Department of Medical Nanotechnology, School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran;2. Mechanic of Agriculture Engineering Department, Roudehen Branch, Islamic Azad University, Roudehen, Iran;1. Unidad de Investigaciones, Banco de la República, Bogotá, Colombia;2. Departamento de Modelos Macroeconómicos, Banco de la República, Bogotá, Colombia;3. Subgerencia de Estudios Económicos, Banco de la República, Bogotá, Colombia;4. Tepper School of Business, Pittsburgh, Pensilvania, Estados Unidos
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 × 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. β-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. α-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.
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