Distinct receptors for Leu- and Met-enkephalin on the metacerebral giant cell of Aplysia

1. The effects of d-Ala²-Leu-enkephalin (DALEU), d-Ala²-Met-enkephalin (DAMET), and FMRFamide on the metacerebral cell (MCC) of Aplysia were determined in current- and voltage-clamp experiments. 2. Distinct receptors exist on this neuron for the three substances. 3. DALEU elicited a depolarizing response due to an inward current but not accompanied by a significant change in membrane conductance. 4. In contrast, DAMET elicited a hyperpolarizing response due to an outward current, also not associated with a significant change in membrane conductance. 5. Both the DALEU and the DAMET responses increased with hyperpolarization, decreased with depolarization, but did not reverse at potentials less than -30 mV. Neither response was sensitive to naloxone. 6. FMRFamide induced a voltage-dependent outward current that reversed at about -76 mV. This neuron was responsive to much lower concentrations of FMRFamide than either of the enkephalins, and the response to FMRFamide appears to be a conductance increase to K⁺. 7. These results suggest that the MCC neuron has distinct receptors for Leuand Met-enkephalin that activate unusual responses of opposite polarity, as well as more usual inhibitory responses to FMRFamide.