Direct and modulatory effects of FMRFamide, SKPYMRFamide and acety1-SKPYMRFamide on LPa2, LPa3, and RPa3 identified neurons of Helix lucorum.

Three neuroactive peptides with an RFamide carboxyl terminal, one a tetrapeptide, FMRFamide, and two heptapeptides, SKPYMRFamide and acetyl-SKPYMRFamide, evoke direct and modulatory effects on identified neurons from left (LPa2, LPa3) and right (RPa3) parietal ganglia of the land snail. Helix lucorum. Local application of tetrapeptide and heptapeptides induce hyperpolarization or outward current when neurons are clamped at the resting potential. The reversal potential of these direct responses is near the potassium equilibrium potential. All investigated FMRFamide-related peptides reduce reversibly the inward current to local acetylcholine (ACh) application onto the neuron soma. Threshold concentrations of peptides for an inhibitory action on ACh-induced current are 0.5-1.0 microM, ID50 = 0.7-1.2 microM, SKPYMRFamide evokes parallel shift to right of ACh dose-response curves increasing the ED50 for ACh but without changing the Hill number. SKPYMRFamide does not change the reversal potential of the ACh-induced inward current. It was concluded that SKPYMRFamide reduces the affinity of ACh for ACh receptor without a change in the number of ligand-binding sites per ACh receptor molecule. FMRFamide-related peptides can reduce the affinity of ACh for cholinergic receptors through inhibition of the molecular mechanism connecting the ACh receptor with its ion channels.