Advanced system for endorphins and opiates already existed in first vertebrates

Endorphins are well known as mediators of pain relief and the feeling of being rewarded. These and several other signal substances do this via four different receptors on nerve cells in the brain and bone marrow. Researchers at Uppsala University have now found that all four receptors existed as far back as the early vertebrates and therefore appeared at least 450 million years ago.

It has long been known that opium, morphine, heroin, and similar so-called opiates can bring about pain relief, euphoria, and sleep (narcosis) but also lead to addiction. In the 1970s it was discovered that this occurs via special receptors in the nerve paths of the body. At almost the same time it was also discovered that the body produces its own substances that can affect the same receptors, thereby producing similar effects. These discoveries were made by several research teams, one of which was led by Lars Terenius at Uppsala University.

The endogenous opiates (endorphins, encephalines, and dynorphin) can also stimulate the body's reward system and thereby affect motivation. Narcotic opiates can therefore lead to addiction and abuse. The effects are mediated mainly by the three opiate receptors named delta, kappa, and my. A fourth similar receptor was discovered in the 1990s.

The evolutionary origin of the opiate system has been shrouded in obscurity. Now Uppsala researchers, led by Dan Larhammar at the Department of Neuroscience, can show that all four receptors existed in the first vertebrates that had jaws. The receptor system existed in both bony fish and all four-limbed vertebrates and emerged in connection with major portions of the genes being quadrupled in the original vertebrate. In other words, the opiate system was already established 450 million years ago.

While humans and other mammals still have the original quartet, several fish species have developed further receptors. For example, the stickleback, with its six opiate receptors, is more complex than humans in this respect. The new findings pave the way for new research on the role of the endorphin system in motivation, rewards, and pain signals in the most distant relatives of humans among vertebrates. What's more, the findings can shed light on how the various opiate receptors came to be specialized for different functions.

This research was funded by the Swedish Research Council and the Carl Trygger Foundation.

Read more on the PNAS website.

For more information please contact Dan Larhammar, phone:+46 (0)18-471 4173; cell phone: +46 (0)706-34 92 14,
e-mail: Dan.Larhammar@neuro.uu.se