Modulatory effects of achatin-I, an Achatina endogenous neuroactive peptide, on responses to 5-hydroxytryptamine.

Achatin-I (Gly-D-Phe-L-Ala-L-Asp) was found in the ganglia of an African giant snail (Achatina fulica Férussac), and proposed as an excitatory neurotransmitter of Achatina neurones. At 3 x 10(-6) the peptide markedly enhanced the fast inward current (Iin) of an Achatina neurone type, TAN (tonically autoactive neurone), produced by the pneumatic pressure ejection of 5-HT. This Iin was facilitated immediately by the achatin-I perfusion, and the facilitation decreased gradually even with the peptide present. The dose (duration)-response curves of the TAN fast Iin on pressure ejection in the absence (control) and presence of achatin-I at 3 x 10(-6) M (n = 8) were analyzed as follows. The ED50 (95% confidence limit) were 59.3 ms (13.9-95.3 ms) for the control, and 36.5 ms (19.5-52.6 ms) for achatin-I. The Emax were 1.06 +/- 0.11 nA for the control, and 1.74 +/- 0.26 nA for achatin-I (P < 0.01 for paired data). Among achatin-I derivatives, achatin-II (Gly-L-Phe-L-Ala-L-Asp) enhanced the TAN fast response to 5-HT, but was ten times weaker than achatin-I. [L-Glu4]achatin-I (Gly-D-Phe-L-Ala-L-Glu) and achatin-I amide (Gly-D-Phe-Ala-L-Asp-NH2) had no facilitatory effect. We propose that achatin-I is a neuromodulator as well as a neurotransmitter for Achatina giant neurones.