PHAR 5091.003

Course Name: Historical Perspectives of Receptor Theory

Course Director: Dr. William Clarke

Course Content:

This course will consist of critical evaluation by the student of the primary literature focusing on papers that have had a major impact on receptor theory. Upon completion of the course students will have a detailed understanding of the evolution of receptor theory. The papers to be evaluated include:

1. Stephenson RP (1997) A modification of receptor theory. 1956. Br J Pharmacol 120:106-20; discussion 103-5.
2. Furchgott RF (1966) The use of ß-haloalkylamines in the differentiation of receptors and in the determination of dissociations constants of receptor-agonist complexes., in Advances in Drug Research (Harper NJ and Simmonds AB eds) pp 21-55, Academic Press, San Diego.
3. del Castillo J and katz B (1957) Interaction at end-plate receptors between different choline derivatives. Proc. R. Soc London B Biol. Sci. 146:369-381.
4. Costa T, Ogino Y, Munson PJ, Onaran HO and Rodbard D (1992) Drug efficacy at guanine nucleotide-binding regulatory protein-linked receptors: thermodynamic interpretation of negative antagonism and of receptor activity in the absence of ligand. Mol Pharmacol 41:549-60.
5. De Lean A, Stadel JM and Lefkowitz RJ (1980) A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor. J Biol Chem 255:7108-17.
6. Kenakin TP and Beek D (1980) Is prenalterol (H133/80) really a selective beta1 adrenoceptor agonist? Tissue selectivity resulting from differences in stimulus-response relationships. J Pharmacol Exp Ther 213:406-13.
7. Katz B and Thesleff S (1957) A study of the 'desensitization' produced by acetylcholine at the motor end-plate. J Physiol (Lond) 138:63-80.
8. Neubig RR, Gantzos RD and Thomsen WJ (1988) Mechanism of agonist and antagonist binding to alpha 2 adrenergic receptors: evidence for a precoupled receptor-guanine nucleotide protein complex. Biochemistry 27:2374-84.
9. Ross EM, Maguire ME, Sturgill TW, Biltonen RL and Gilman AG (1977) Relationship between the beta-adrenergic receptor and adenylate cyclase. J Biol Chem 252:5761-75.
10. Samama P, Cotecchia S, Costa T and Lefkowitz RJ (1993) A mutation-induced activated state of the beta 2-adrenergic receptor. Extending the ternary complex model. J Biol Chem 268:4625-36.
11. Morisset S, Rouleau A, Ligneau X, Gbahou F, Tardivel-Lacombe J, Stark H, Schunack W, Ganellin CR, Schwartz JC and Arrang JM (2000) High constitutive activity of native H3 receptors regulates histamine neurons in brain. Nature 408:860-4.
12. Jordan BA and Devi LA (1999) G-protein-coupled receptor heterodimerization modulates receptor function. Nature 399:697-700.

Grading: Students will read each paper and discuss critically the contents of the papers with the course director. For each paper, the student will provide a brief (1-2 pages, double spaced) report highlighting the important findings and their significance to receptor theory. It is expected that students will do some additional reading of the primary literature as needed to familiarize themselves with the paper under discussion. Students will be graded based upon the one-page summaries and the quality of discussions of the papers with the course director. Grading will be on a lettered scale.

Pre-requisites: Principles of Pharmacology

Credit Hours: 1 credit

When offered: Anytime