DIRECT AND MODULATORY EFFECTS OF FMRFAMIDE, SKPYMRFAMIDE AND ACETYL-SKPYMRFAMIDE ON LPA2, LPA3, AND RPA3 IDENTIFIED NEURONS OF HELIX-LUCORUM

Three neuroactive peptides with an RFamide carboxyl terminal, one a te trapeptide, FMRFamide, and two heptapeptides, SKPYMRFamide and acetyl- SKPYMRFamide, evoke direct and modulatory effects on identified neuron s from left (LPa2, LPa3) and right (RPa3) parietal ganglia of the land snail, Helix lucorum. Local application of tetrapeptide and heptapept ides induce hyperpolarization or outward current when neurons are clam ped at the resting potential. The reversal potential of these direct r esponses is near the potassium equilibrium potential. All investigated FMRFamide-related peptides reduce reversibly the inward current to lo cal acetylcholine (ACh) application onto the neuron soma. Threshold co ncentrations of peptides for an inhibitory action on ACh-induced curre nt are 0.5-1.0 mu M, ID50 = 0.7-1.2 mu M. SKPYMRFamide evokes parallel shift to right of ACh dose-response curves increasing the EDS, for AC h but without changing the Hill number. SKPYMRFamide does not change t he reversal potential of the ACh-induced inward current. It was conclu ded that SKPYMRFamide reduces the affinity of ACh for ACh receptor wit hout a change in the number of ligand-binding sites per ACh receptor m olecule. FMRFamide-related peptides can reduce the affinity of ACh for cholinergic receptors through inhibition of the molecular mechanism c onnecting the ACh receptor with its ion channels.