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Derek Lowe The 2002 Model

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Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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January 19, 2004

There'd Better Not Be an Argon Receptor

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Posted by Derek

Signaling between cells is weirder than we used to think it was. There's a hardy perennial, all right - that sentence could have been written whenever you like for the past fifty years or so. But the surprises keep on coming. Some of the most intense communication needs are between neurons, as you'd expect, and it looks like nature has taken advantage of all kinds of things to achieve greater bandwidth.

Everyone now learns about nitric oxide and its effects when they study physiology. The thought of a toxic gas as a neurotransmitter was a tough one to deal with at first, but the evidence was overwhelming. Then in the 1990s, two more oddities were proposed in the same category, and they're even more poisonous: hydrogen sulfide and carbon monoxide. Comments of the "You have to be kidding" sort greeted the initial work in this field, but the nitric oxide work had opened the door. It now appears that these two are, indeed, important signaling molecules in the brain.

Hydogen sulfide has a number of physiological effects, other than poisoning you (or, in lower concentrations, making you choke on its delightful aroma.) It seems to act on smooth muscle along with nitric oxide (now, there's a combination I would go out of my way to avoid breathing), and it also seems to have a role in laying down long-term memory. Carbon monoxide also seems to have a number of different functions - it's vasoactive, like its gaseous partners, but also seems to be involved in the immune response and in cellular protection and repair.

Taking up in the same way as the nitric oxide research, which has stimulated a huge amount of drug discovery work over the years, people are now trying similar tricks with these new gases. Look for more and more work on these in the drug industry as their mechanisms get fleshed out.

What's next? Well, it's not impossible that some other small-molecule gases have their own pathways, too. These things have properties that aren't shared by any other molecules, and perhaps they're being put to use. Ammonia, sulfur dioxide, and nitrous oxide have all been proposed as candidates. Thinking along those lines, I have to wonder about the small alkyl derivatives like methylamine and dimethyl sufide, too. Why not? But if someone gets around to claiming chlorine or the other halogens, I'm going to start to wonder. And if there turns out to be a physiological role for the noble gases, I'd start to suspect that Einstein was wrong: maybe God's approach to scientific laws is malicious after all. It would explain a lot, now that I think about it. . .

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