From “mysterious opiate effect” to the body’s own opioid system
The problem: How could the brain respond to morphine-like compounds?
Before the 1970s, researchers knew that opiate drugs could produce powerful effects in the nervous system. The unanswered question was why the body had receptors that recognised these substances so precisely.
The solution came from studying brain tissue. In 1975, John Hughes, Hans Kosterlitz and colleagues reported the identification of two related pentapeptides, Met-enkephalin and Leu-enkephalin, that produced opiate-like activity in laboratory studies. Their discovery showed that opioid receptors were not simply waiting for morphine. They were part of a built-in communication system.
This was a major shift in biology. Pain control was no longer viewed only as an external drug effect. Researchers could now study the body’s own opioid messages, how they were released and how quickly they were broken down.
You can think of the discovery as finding a factory’s internal access cards. The opioid receptor was the lock; met-enkephalin was one of the body’s natural keys.
Where is met-enkephalin produced?
The problem: Is met-enkephalin only a brain chemical?
No. Met-enkephalin is widely distributed across central and peripheral tissues.
It is produced from larger precursor proteins, particularly proenkephalin, which acts like a long master blueprint. Enzymes cut that blueprint into smaller active peptides, including met-enkephalin and other enkephalin-related fragments.
Research has identified enkephalin signalling in areas including:
- Brain: The cortex, striatum, hippocampus, hypothalamus, amygdala and periaqueductal grey.
- Spinal cord: Particularly regions involved in processing incoming pain signals, including the dorsal horn.
- Adrenal medulla: The inner region of the adrenal gland, where stress-related catecholamine signalling is coordinated.
- Gastrointestinal tract: Enteric nerves and other gut-associated cells.
- Peripheral nerves and tissues: Including autonomic and visceral pathways.
- Immune cells: Certain immune cells can produce or respond to opioid peptides, creating a separate area of immune-signalling research.
The key point is distribution. Met-enkephalin is not a single-purpose “pain peptide”. It is more like a message used by several departments in the body’s communication network.
