Sensitivities of Achatina giant neurones to putative amino acid neurotransmitters.
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.
Takeuchi
H
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Department of Physiology, Gifu University School of Medicine, Japan.
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004553:Electric Conductivity / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011963:Receptors, GABA-A / Q000145:classification / Q000502:physiology*; D018080:Receptors, GABA-B; D012908:Snails; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018377:Neurotransmitter Agents; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D001418:Baclofen