Mammalian neuronal actions of FMRFamide and the structurally related opioid Met-enkephalin-Arg6-Phe7.

Since the enkephalins were first isolated a number of opioid peptides have been discovered, including a heptapeptide with the sequence Tyr-Gly-Gly-Phe-Met-Arg-Phe (Met-enkephalin-Arg6-Phe7). The heptapeptide was first isolated from chromaffin granules in bovine adrenal medulla, but using immunochemical techniques it has now been identified in human, rat and bovine brains. The C-terminal tetrapeptide of this molecule (Phe-Met-Arg-Phe) occurs in amidated form as the molluscan peptide FMRFamide. Antisera raised against FMRFamide have revealed immunoreactive material in the brains of several vertebrate species, including the rat where it occurs in nerve cell bodies and terminals. I now report that ionophoretically applied FMRFamide has an excitatory effect on rat medullary neurones which is unaffected by the opiate antagonist naloxone. In contrast, Met-enkephalin-Arg6-Phe7 and leucine-enkephalin (Leu-enkephalin) have predominantly depressant effects, which suggests that FMRFamide acts at a separate receptor.