Thursday, August 10, 2006

I work for peanuts

I visited NYC after work last Saturday and supped at Spice, a Thai restaurant chainlet with a couple of locations in the city (I was on the Upper East Side). The decor was mod and minimalist and the food was great, but we limited our selection because one of my friends is highly allergic to peanuts.
Nature News ran an article a few weeks back that sheds a little more light on the mechanism behind anaphylactic shock. This is the most severe form of allergy, leading to a drop in blood pressure that is fatal if left untreated. We can treat someone who is in shock with a shot of epinephrine ("epi"), but this is more of a patchup; it doesn't get at the root of the problem and it can't prevent shock.
Here's the paper:
J. Clin. Invest. 2006, 116, 2244-2251.
In a nutshell (ha ha), the researchers confirmed previous reports that nitric oxide pathways are responsible, but the source of the nitric oxide wasn't the one they were expecting. They also pinpoint an often-studied signaling pathway (the PI 3-kinase pathway) as one of the orchestrators behind the whole nitric oxide-mediated shock response.
The PI 3-kinase pathway is involved in a large number of fundamental processes in our cells. A kinase is an enzyme that puts a tag (a phosphate group) on some other protein. The body uses phosphate groups as switches, adapters or handles for a ridiculous number of things. It's one of the ways the body physically transfers and amplifies a message. The authors conclude that it might be useful to look at the PI 3-kinase pathway as a way to intercept the shock response.
To demonstrate the involvement of PI 3-kinase, the researchers used wortmannin, my personal favorite inhibitor of PI 3-kinase. Wortmannin is a natural product made by fungi and it reacts with the business end of PI 3-kinase. For the mechanistically minded, I've included a figure.

The PI 3-kinase enzyme has a critical lysine involved in the phosphate transfer reaction, and wortmannin knocks that bad boy out of commission.



At 5:49 PM, Anonymous Jason Fehr said...

I had a guy once who anaphylaxed -to- epinephrine (some preservative in the mixture), thus complicating the treatment somewhat. I thought this was hilarious, he didn't seem to agree.

I hadn't heard about that pathway, it would be nice to make some progress there.

At 6:10 PM, Anonymous Ryan said...

"Anaphylactic shock" would be a great name for a band. And it opens the door for irony should someone fall victim to said disease during a show. Is that what happened to the kid in freaks and geeks?

At 6:14 PM, Blogger Good Guy said...

Good info.

Herbal Man


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