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 steroisomers, only achatin-I markedly, and [D-Ala3]achatin-I slightly, induced a slow inward current (I(in)) 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-1 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, deviated from 1.0. E(max) values of achatin-I for producing I(in), 4.2-6.3 nA, were significantly greater than those of [D-Ala3]achatin-I, 1.8-3.4 nA. I(in) 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 (3.0 x) state, indicating that the current was produced by the g increase in response to Na+. However, the I(in) was partially blocked by tetrodotoxin 10(-4) M. We propose that achatin-I is an excitatory neurotransmitter on Achatina neurones.