Synthesis of achatin-I (Gly- d-Phe- l-Ala- l-Asp) analogs having dehydrophenylalanine or aminoisobutyric acid residue at position 2, and their effects on Achatina giant neurons

• Published in: General pharmacology 1997-02, Vol.28 (2), p.265-267
• Main Authors: Emaduddin, Muhammad, Takeuchi, Hiroshi, Jain, Ratan Mani, Chauhan, Virender Singh
• Format: Article
• Language: English
• Subjects: achatin-I (Gly- d-Phe- l-Ala- l-Asp); Achatina fulica; analogs; Animals; Biological and medical sciences; Freshwater; Fundamental and applied biological sciences. Psychology; giant neuron; Invertebrate Hormones - pharmacology; Isolated neuron and nerve. Neuroglia; Neurons - drug effects; Neuropeptide; Neuropeptides - chemical synthesis; Neuropeptides - pharmacology; Neurotransmitter Agents - pharmacology; snail ( Achatina fulica Férussac); Snails; Vertebrates: nervous system and sense organs; α-aminoisobutyric acid; β-dehydrophenylalanine
• ISSN: 0306-3623; 1879-0011
• DOI: 10.1016/S0306-3623(96)00170-X

1. 1. Achatin-I (Gly- d-Phe- l-Ala- l-Asp), a neuroactive tetrapeptide having a d-phenyl-alanine residue, has been proposed to be an excitatory neurotransmitter of Achatina giant neurons. It was revealed that the d-Phe 2 residue is essential for bioactivity of achatin-I, which seems to adopt β-turn conformation. In the present study, in order to investigate the structure-activity relationships of achatin-I and its derivatives, the two highly constrained analogs of achatin-I, [Δ ZPhe 2]achatin-I (Gly-Δ ZPhe- l-Ala- l-Asp) (Δ ZPhe: (Z)-α,β-dehydrophenylalanine) and [Aib 2]achatin-I (Gly-Aib- l-Ala- l-Asp) (Aib: α-aminoisobutyric acid), were synthesized, and their effects on the two identifiable Achatina giant neuron types, PON (periodically oscillating neuron) and v-RCDN (ventral-right cerebral distinct neuron), were examined in comparison with those of achatin-I under voltage clamp. 2. 2. Achatin-I ( n = 6), ejected onto the neurone by brief pneumatic pressure (2 kg/cm 2, 400 ms, 10 −3 M, at 10-min intervals), produced an inward current ( I i ) on PON. The I i value (mean ± SEM) was 0.44±0.03 nA. The interval between the achatin-I ejection and the I i peak was 14.74±3.15 s ( n=6). [Δ ZPhe 2]achatin-I ( n=6) and [Aib 2]achatin-I ( n=6) had no effect on this neuron type. 3. 3. On the other hand, achatin-I ( n=10) and [Δ ZPhe 2]-achatin-I ( n=10), ejected by brief pressure, produced an I in on v-RCDN. The I in values were 0.85±0.07 nA for achatin-I and 0.48±0.05 nA ( p