INHIBITORY-ACTION OF SKPYMRFAMIDE ON ACETYLCHOLINE-RECEPTORS OF HELIX-ASPERSA NEURONS - ROLE OF 2ND MESSENGERS

1. SKPYMRFamide, a novel FMRFamide-like endogenous peptide reversibly decreases excitatory responses (depolarization and inward current) evo ked by local ionophoretic application of acetylcholine (ACh) onto the soma of identified neurons F1, F2, F4 and F5/6 of the land snail, Heli x aspersa. 2. Threshold concentrations of SKPYMRFamide for an inhibito ry action on ACh-induced responses are 0.5-1 mu moll(-1). This modulat ory action of peptide is dose- and time-dependent. 3. It is concluded that SKPYMRFamide inhibits ACh receptors through activation of specifi c binding sites on the plasma membrane. 4. The possible role of differ ent second messengers in the modulatory influence of SKPYMRFamide on A Ch receptors was tested using 13 modulators of different second messen ger systems. 5. The results indicate that SKPYMRFamide may inhibit ACh receptors through activation of one or more of the following systems: phospholipases C, A(2), NO-synthase, soluble guanylate cyclase and li poxygenases which elevate basal intracellulal levels of NO, cGMP, arac hidonic acid, acyclic eicosanoids, inositol-1,4,5-trisphosphate (I(1,4 ,5)P-3), I(1,4,5)P-3-dependent Ca2+-mobilization followed by activatio n of calmodulin and Ca2+/calmodulin-dependent protein kinase II. Prote in kinases A, C and cyclic eicosanoids do not appear to participate in modulatory action of SKPYMRFamide.