Slow inward current induced by achatin-I, an endogenous peptide with a D-Phe residue.
Following a preliminary report on the isolation of a neuroactive tetrapeptide, achatin-I (Gly-D-Phe-L-Ala-L-Asp) that has a D-phenylalanine residue, from the Achatina fulica ganglia, the pharmacological features of this peptide on Achatina giant neurones were now worked out in detail. Of the eight possible stereoisomers, only achatin-I markedly, and [D-Ala3]achatin-I slightly, induced a slow inward current (Iin) with an increase in membrane conductance (g) of the identifiable neurones, tonically autoactive neurone (TAN), dorsal-right cerebral distinct neurone (d-RCDN) and periodically oscillating neurone (PON) which had been tested previously. Of 23 types of neurones tested, 10 types including the three mentioned were excited by achatin-I, whereas no neurone was inhibited. The ED50 of achatin-I for the neurones tested were 0.2-2.7 x 10(-5) M, and that for PON was the lowest. The Hill coefficients of achatin-1. 0.62-0.80, derived from 1.0 Emax values of achatin-I for producing Iin, 4.2-6.3 nA, were significantly greater than those of [D-Ala3]achatin-I, 1.8-3.4 nA. Iin of TAN and d-RCDN induced by achatin-I was blocked in the Na(+)-free state, but unaffected in the Ca2(+)-free (replaced with Co2+), Cl(-)-free or K(+)-enriched (3.0X) state, indicating that the current was produced by the g increase in response to Na+. However, the Iin was partially blocked by tetrodotoxin 10(-4) M. We propose that achatin-I is an excitatory neurotransmitter on Achatina neurones.
Kim
K H
KH
Department of Physiology, Gifu University School of Medicine, Japan.
Takeuchi
H
H
Kamatani
Y
Y
Minakata
H
H
Nomoto
K
K
D000595:Amino Acid Sequence; D000818:Animals; D004594:Electrophysiology; D005724:Ganglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D010649:Phenylalanine / Q000502:physiology*; D012908:Snails / Q000378:metabolism*; D012964:Sodium / Q000502:physiology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D007473:Ion Channels; D009479:Neuropeptides; D018377:Neurotransmitter Agents; C059927:achatin I; D010649:Phenylalanine; D012964:Sodium