After doing a whole bunch of cutting-edge papers for the class its time to go back in time a bit (like 1998 is ancient but anyways) and do an oldie-but-goodie. This particular paper, “Effector Pathway-Dependent Relative Efficacy at Serotonin Type 2A and 2C Receptors: Evidence for Agonist-Directed Trafficking of Receptor Stimulus”, Berg et al., 1998 Molecular Pharmacology (Free at Mol Pharm) isn’t really a citation classic (with 278 citations according to google scholar), yet, it marks a very significant moment in GPCR pharmacology. I like this paper for two reasons: 1) It moved a major, emerging pharmacology theoretical framework forward toward experimental discovery and 2) I am very fond of the first and last authors.
First to my fondness for the first and last authors, Kelly Berg and Bill Clarke. Bill and Kelly are professors in the Department of Pharmacology at The University of Texas Health Science Center at San Antonio (UTHSCSA). It so happens that I did my PhD in that very department (I started there in 1998). The very first class I took was Bill Clarke’s Principles of Pharmacology course. When I joined the department I was quite sure I wanted to be a pharmacologist but this course drove that point home for me in ways that are difficult to describe. The course was mainly taught by Bill and Kelly (who happen to be married) with Bill doing most of the teaching on basic principles and Kelly doing the teaching on molecular signaling through GPCRs. While I learned an enormous amount about basic pharmacological principles and the ins-and-outs of GPCR signaling in the class my main memories are of the passion for teaching and graduate education that they both passed on to all of us throughout the semester. I like to think that my teaching style came mostly from the two of them and while I am sure I have not yet lived up to their level of excellence, their example consistently gives me a goal to shoot for. In this class I like to use this paper to transition from screening technologies back to pharmacological principles largely because it reminds me to try to live up to what BIll and Kelly imparted to me through their course.
Okay, enough nostalgia, onto the paper… Continue reading