Regulation of alpha-1B adrenergic receptor localization, trafficking, function, and stability

Life Sci. 2003 Dec 5;74(2-3):379-89. doi: 10.1016/j.lfs.2003.09.024.


The alpha-1 adrenergic receptors (alpha(1)ARs) play important roles in normal physiology and in many disease states, and understanding their signaling pathways and regulatory mechanisms is thus of considerable relevance, in particular for identifying pharmacological targets for therapeutic modulation. The expression, function, localization, trafficking, and stability of these receptors are all subject to complex regulation by diverse molecular mechanisms. This article highlights recent studies from our laboratory and others focused on the localization and trafficking of the alpha-1B adrenergic receptor (alpha(1B)AR) subtype and on changes in its stability that are likely to be involved in regulating receptor expression. The role(s) of protein kinase C in alpha(1B)AR sequestration, endocytosis, and extracellular signal-regulated kinase (ERK) activation are summarized, and evidence for alpha(1B)AR localization in caveolae/rafts is presented. Receptor structural domains involved in the multiple steps and mechanisms of agonist-induced desensitization are described. Finally, aspects of alpha(1B)AR structural stability that appear to control its drug-induced up- and down-regulation are discussed. Our understanding of regulation for the alpha(1B)AR subtype provides a model for studies of the differential regulation of the other alpha(1)AR subtypes and may lead to identification of new molecular targets for therapeutic intervention in a variety of disease states.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Caveolae / metabolism
  • Down-Regulation / genetics
  • Down-Regulation / physiology
  • Humans
  • Membrane Microdomains / metabolism
  • Mitogen-Activated Protein Kinases / physiology
  • Protein Kinase C / metabolism
  • Protein Kinase C / physiology
  • Receptors, Adrenergic, alpha-1 / drug effects
  • Receptors, Adrenergic, alpha-1 / genetics
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Receptors, Adrenergic, alpha-1 / physiology


  • ADRA1B protein, human
  • Receptors, Adrenergic, alpha-1
  • Protein Kinase C
  • Mitogen-Activated Protein Kinases