Historical review: a brief history and personal retrospective of seven-transmembrane receptors.

Journal Article (Journal Article)

Pharmacologists have studied receptors for more than a century but a molecular understanding of their properties has emerged only during the past 30-35 years. In this article, I provide a personal retrospective of how developments and discoveries primarily during the 1970s and 1980s led to current concepts about the largest group of receptors, the superfamily of seven-transmembrane (7TM) receptors [also known as G-protein-coupled receptors (GPCRs)]. Significant technical advances such as the development of methods for radioligand binding, solubilization and purification of the beta(2)-adrenoceptor and other adrenoceptors led to the cloning of receptor genes and the discovery of their 7TM architecture and homology with rhodopsin. A universal mechanism of receptor regulation by G-protein-coupled receptor kinases (GRKs) and arrestins, originally discovered as a means of "desensitizing" G-protein-mediated second-messenger generation, was subsequently found to mediate both receptor endocytosis and activation of a growing list of signaling pathways such as those involving mitogen-activated protein kinases. Numerous opportunities for novel therapeutics should emerge from current and future research on 7TM receptor biology.

Full Text

Duke Authors

Cited Authors

  • Lefkowitz, RJ

Published Date

  • August 2004

Published In

Volume / Issue

  • 25 / 8

Start / End Page

  • 413 - 422

PubMed ID

  • 15276710

International Standard Serial Number (ISSN)

  • 0165-6147

Digital Object Identifier (DOI)

  • 10.1016/j.tips.2004.06.006


  • eng

Conference Location

  • England