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Posted

I just read that someone won the Nobel Prize for work on the Fight or Flight mechanism. The research was on the "G protein coupled receptors". Does anyone know if this has anything to do with us.

Posted

Only on a pretty basic level... basically, G protein coupled receptors (GPCRs) are involved in cell-to-cell signaling - the receptor receives a signal (perhaps a hormone or a neurotransmitter, for example, though there are others too), then triggers a cascade of reactions via the G protein coupled complex. This cascade changes something in the cell - perhaps gene regulation (which RNA is produced from DNA) or translation (how proteins are made from RNA). They're a very broad class of receptors with a lot of different purposes. They are (apparently, though I hadn't known this) the target of ~40% of pharmaceuticals, so understanding their basic structure and function is very important for medicine.

(edited to add - the Nobel is usually for something fundamentally basic and important like this, rather than direct applications, though those exist too - like stuff involving insulin. From a fight/flight/ANS point of view, GPCRs are involved in things like hormone/neurotransmitter reception, so they probably are involved in our sympathetic nervous system regulation via their reception of things like norepinephrine. If this is totally unclear, let me know; sometimes it's hard for me to take my "biology grad student" hat off :^)

  • 2 weeks later...
Posted

So... the guy who won the prize (well, one of the two) just gave a talk here at my university, so I stopped in. Lots of really high-level stuff (I would have been lost in seconds without having a lot of background), but some directly relevant stuff too! If folks want more information about the general topic (rather than just the stuff he did at the end), message me.The

The one really applicable part to us is the end, where he talked about the way that G protein-coupled receptors (these receptors that bind things like epinephrine, but also bind things like beta blockers) are specific as to what binds to them. They have two levels (kind of like two floors in a house) of the "pocket" that holds the drug or molecule. The first level - the highest one - determines what molecule can bind - the "specificity" of the receptor; the molecule has to pass through here to be effective. Some of these receptors are more picky than others - it depends on how wide their pocket is. The second level - the lower one, and the one where the molecule actually sits - determines how active the receptor is once that molecule sits there - basically, its "efficacy" - how strongly it responds to the drug or molecule.

Specific beta blockers like atenolol and specific other drugs like albuterol sit in the second level, but many of them extend a "tail" up to the first level, so they are specific even when they are past the part of the pocket that is more picky. This is why albuterol only hits beta-2 receptors and not beta-1 receptors. Other nonselective beta blockers like propranolol and other drugs don't stick out into the first level when they're sitting in the second level, so as long as they can sneak into the receptor past the picky part of the pocket, they're good. This is why propranolol affects things like breathing - it hits both the beta-1 receptors (which deal with the heart rate, etc) and the beta-2 receptors (which is why it's bad for breathing).

Sometimes other types of receptors - like muscarinic receptors - make the molecule or drug "float" around for a bit, so even if it doesn't have the magic tail extending into the picky part of the receptor, the receptor still has a chance to say "nope, wrong molecule" even though these receptors are generally more generalized.

He also said a bit during the Q+A at the end - something about epinephrine and norepinephrine-binding G protein-coupled receptors being nonselective - they bind anything that looks like epinephrine or norepinephrine and target a wide variety of downstream effects? And that vasopressin receptors are more selective - they only target a certain set of cellular machinery.

Anyways, fun talk!

Posted

No problem! It's really cool when someone like him who does basic research (as opposed to directly-medical research) finds out such cool stuff. Nice guy, too - he was super-shy and said he hadn't spoken in front of 500 people before :^)

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