title: The Molecular Pharmacology of G Protein Signaling Then and Now: A Tribute to Alfred G. Gilman.
abstract: The recent, unfortunate death of Alfred G. ("Al") Gilman, M.D., Ph.D., represents a sad signpost for an era spanning over 40 years in molecular pharmacology. Gilman's discoveries, influence, and persona were dominant forces in research and training in pharmacology. Here, we review the progression of ideas and knowledge that spawned early work by Gilman and collaborators (among them, one of the authors) and later efforts (including those of the other author) that have recently yielded a comprehensive and precise structural understanding of fundamental topics in pharmacology: the binding of ligands to G protein-coupled receptors (GPCRs) and the interaction of GPCRs with heterotrimeric G proteins and effector molecules. Those data provide new and important insights into the molecular basis that underlies affinity and efficacy, two of the most important features of drug action, which represent the latest chapter in the saga that Al Gilman's work helped launch.
authors.affiliation: Department of Pharmacology (R.K.S., P.A.I.) and Department of Medicine (P.A.I.), University of California, San Diego, La Jolla, California rsunahara@ucsd.edu.
authors.forename: Roger K
authors.initials: RK
authors.lastname: Sunahara
authors.affiliation: Department of Pharmacology (R.K.S., P.A.I.) and Department of Medicine (P.A.I.), University of California, San Diego, La Jolla, California.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Insel
mesh_terms: D000262:Adenylyl Cyclases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001319:Authorship; D001671:Biochemistry / Q000193:education / Q000266:history*; D000242:Cyclic AMP / Q000502:physiology*; D054768:G-Protein-Coupled Receptor Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D049673:History, 20th Century; D049674:History, 21st Century; D006801:Humans; D007700:Kinetics; D007857:Leadership; D008024:Ligands; D008954:Models, Biological; D062346:Molecular Medicine / Q000193:education / Q000266:history*; D009307:National Academy of Sciences, U.S.; D009613:Nobel Prize; D010599:Pharmacokinetics; D010600:Pharmacology / Q000193:education / Q000266:history*; D015290:Second Messenger Systems / Q000187:drug effects; D014481:United States
chemical_list: D008024:Ligands; D000242:Cyclic AMP; D054768:G-Protein-Coupled Receptor Kinases; D000262:Adenylyl Cyclases