Leu-enkephalin

Where it comes from

Made in

The same neurons as met-enkephalin, and the dynorphin neurons, whose peptides begin with it

Sent out by

With met-enkephalin

Acts on

• Pain and reward circuits
• Gut

What it does

• Does what met-enkephalin does, with a little more delta selectivity ²
• The first five residues of every dynorphin, so each prodynorphin peptide carries a leu-enkephalin inside it
• Gone within seconds in blood, cut by aminopeptidases and by the enkephalinases ¹

In medicine

• No medicine copies it. Racecadotril, which spares the gut’s enkephalins, protects it alongside met-enkephalin, and the effect is credited to the pair rather than to either alone
• It is not measured in practice. Antisera raised against the five residues cannot tell free leu-enkephalin from the dynorphins, every one of which begins with exactly that sequence

Beyond the body’s own use

• Stable delta-selective agonists modelled on it have reached human trials for pain and for depression and none is approved; the prototype SNC80 caused convulsions in rats and monkeys, which the class has had to be designed around ³
• Leu-enkephalin itself is not approved anywhere and is not taken outside medicine: swallowed or injected it is gone in seconds ¹
• What is unknown is whether the body uses it apart from met-enkephalin. Proenkephalin makes four met-enkephalins for every leu-enkephalin, and no cell is known that releases one without the other ²