October 10, 2012 11:34 am
Everyone Believed Cell Receptors Existed, But Chemistry Nobelists Figured Out That They Actually Did
Carried in your blood stream, a vast array of chemical messengers—hormones—tell your body how to behave and how to respond to external forces. A scary sight at night, says the Royal Swedish Academy of Sciences, triggers a shot of adrenaline (along with a range of other hormones), the basis of the fight-or-flight response. But before these chemicals can carry out their work—a boosted heart rate, a rush of energy to your muscles and changes in your airway to help you get more oxygen per breath—they first need to make it into all of the various cells around your body. Figuring out the specifics of how they do this has earned Robert Lefkowitz and Brian Kobilka the 2012 Nobel Prize in Chemistry.
Even before the pair’s work, says The New York Times, scientists assumed that receptors lining the walls of cells were responsible for transporting hormones across the largely impermeable barriers. The specific details explaining how those receptors work (their shape, their genetic blueprint, their specific functionality, and even their existence) were still up in the air. Lefkowitz and Kobilka’s work over the years, starting back in the 1960s when Lefkowitz was just a student, led the charge in cracking those problems. The two scientists’ research focused on a class of cellular receptors known as G-protein coupled receptors, or seven-transmembrane domain receptors, for the fact that they crisscross the cell wall seven times.
Everyone had realized, for decades (more like centuries), that cells had to be able to send signal to each other somehow. But how was this done? No matter what, there had to be some sort of transducer mechanism, because any signal would arrive on the outside of the cell membrane and then (somehow) be carried across and set off activity inside the cell. As it became clear that small molecules (both the body’s own and artificial ones from outside) could have signaling effects, the idea of a “receptor” became inescapable. But it’s worth remembering that up until the mid-1970s you could find people – in print, no less – warning readers that the idea of a receptor as a distinct physical object was unproven and could be an unwarranted assumption. Everyone knew that molecular signals were being handled somehow, but it was very unclear what (or how many) pieces there were to the process. This year’s award recognizes the lifting of that fog.
As Lowe mentions in his blog, GPCRs underlie the bulk of modern pharmaceutical research. A 2004 article from the American Chemical Society said:
If you had to make a wild guess about the target of a certain drug, your best odds are with “G-protein coupled receptor.” Drugs targeting members of this integral membrane protein superfamily, which transmit chemical signals into a wide array of different cell types, represent the core of modern medicine. They account for the majority of best-selling drugs and about 40% of all prescription pharmaceuticals on the market. Notable examples include Eli Lilly’s Zyprexa, Schering-Plough’s Clarinex, GlaxoSmithKline’s Zantac, and Novartis’s Zelnorm.
Upon hearing of his Nobel win, Lefkowitz told the Times, he had to rejig what he was going to do with his day.
“I was going to get a haircut,” Dr. Lefkowitz said, “which if you could see me, you would see, is quite a necessity, but I’m afraid that’ll probably have to be postponed.”
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