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.