|Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1992: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1991: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1990: ¥1,200,000 (Direct Cost: ¥1,200,000)
A neuroexcitatory tetrapeptide having a D-phenylalanine residue (Gly-D-Phe-L-Ala-L-Asp), termed achatin-I, has been isolated from the ganglia of an African giant snail (Achatina fulica Ferussac). We demonstrated that achatin-I is acting as an excitatory neurotransmitter and a neuromodulator to Achatina giant neurones, supported partly by this fund in 1990-92.
1. Of the eight possible stereoisomers of achatin-I, only achatin-I showed marked excitatory effects on these giant neurones. Among twenty-three Achatina neurone types tested, the ten types were excited by achatin-I. With these findings, we proposed that achatin-I is acting as an excitatory neurotransmitter of these neurones. The effects of the peptide was due to the membrane permeability increase to Na^+ (in 1990).
2. The structure-activity relationships of achatin-I and its derivatives were studied. Among these compounds, only achatin-I had marked effects, indicating that the effects were not only stereo-specific but also structur
e-specific on these neurones (in 1991).
3. We looked for the drugs antagonistic to the achatin-I excitation by testing the known blockers of the small molecule neurotransmitters. We found that the three histamine (H_1) blockers, triprolidine, homochlorcyclidine and trimeprazine, antagonized the achatin-I excitation. These effects were not due to the effects of histamine (H_1) antagonists, since the majority of H_1 blockers tested were not effective on the achatin-I excitation. The known blockers of other small molecule neurotransmitters including H_2 blockers showed no effect on the achatin-I excitation.
A component of the excitation caused by 5-hydroxytryptamine (5-HT) was facilitated by achatin-I at 3 x 10^<-6> M, which was lower than its ED_<50> for the direct excitation. Of the neuroactive peptides originally isolated from Mollusca, the effects of oxytocin and APGW-amide were suppressed by achatin-I, whereas those of FMRFamide were facilitated. Based on these results, it is considered that achatin-I is acting to the Achatina neurones also as a neuromodulator (in 1992). Less