All sorts of odd things have turned out to be neurotransmitters, that's for sure. I wrote about this over a year ago, in a post about hydrogen sulfide, of all things, and its role in the brain.

Well, there's another odd one that's been uncovered. And like hydrogen sulfide (or carbon monoxide, also a neurotransmitter, if you can believe it), it's a molecule that we already know about. Heck, we already know that it does all sorts of things to the brain. We just didn't know that the brain could make its own. Are you ready?

It's morphine. Who would have thought? The brain certainly has plenty of opioid receptors, but it was thought that some classes of short peptides (enkephalins and endorphins) were the endogenous ligands that bound to them. Morphine and the other alkaloids of its family were supposed to be the interlopers from the plant kingdom that could mimic our peptides, but it appears that story is going to need revisions.

A group at Halle (Germany) has done the detective work here. There were reports over the years of small amounts of morphine in mammalian cells, but no one was sure what to make it them. With modern analytical techniques, everything is contaminated: you can find little bits of almost anything you're looking for. Morphine had shown in up things like lettuce, milk, and rat chow before, in trace amounts, so who could say?

The connection seems solid now. The Halle group took human neuroblastoma cells in culture and gave them isotopically labeled dopamine as a starter. That's the (distant) precursor for morphine in poppies, and the cells used it to spit out small amounts of isotopically labled morphine. The same went for a number of other known morphine intermediates (but not quite all of them.) It appears that human cells use a very similar set of reactions to make morphine, but differ from the plant route at one key step.

The authors note, dryly, that "The function of endogenous morphine is still a matter of discussion." I'll bet it is. Why on earth do we make morphine when we have the enkephalins and endorphins? But it's at least a 19-step synthesis for the cells, and you can be sure that they're not going through that for nothing. The paper points out that identifying the various enzymes involved in the synthesis could provide some interesting targets for CNS drug discovery, and I'll bet that they're right about that, too.