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Friday, May 9, 2008

One Consuming Interest

Over the last several years, one of my consuming interests has been to understand how our cellular receptors function on the molecular level. Somewhat surprisingly, there is a rather simple two-state, acid-base model that accounts for a remarkable number of experimental findings.

These include everything from the Weber-Fechner law (see
link) to the redox sensitivities of many receptors (see
Activation of G Protein-Coupled Receptors Entails Cysteine Modulation of Agonist Binding, J. Molecular Structure (Theochem), 430/1-3: 57-71 (1998) and Molecular dynamics of a biophysical model for beta-2-adrenergic and G protein-coupled receptor activation Journal of Molecular Graphics and Modelling 25: 396-409 (2006), for a picture of this model - Click here then also click on the picture). Over several years, I've tested many of the predictions from this model and found that it predicts and continues to explain a number of interesting findings. These include rapid receptor desensitization or tachyphylaxis (see link) and a method for preventing this desensitization (see link) and the phenomenon of "spare receptors", which is an old conundrum in pharmacology (see link).

Understanding how our receptors work at the molecular level is an awe inspiring undertaking, because these are the molecules that link our thoughts and senses to the universe. Understanding how they function may open new frontiers for us to truly understand our place in the cosmos.

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