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

Myron Lee Toews, Steven C. Prinster, Nancy A. Schulte

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

The alpha-1 adrenergic receptors (α1ARs) 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 (α1BAR) 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 α1BAR sequestration, endocytosis, and extracellular signal-regulated kinase (ERK) activation are summarized, and evidence for α1BAR 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 α 1BAR structural stability that appear to control its drug-induced up- and down-regulation are discussed. Our understanding of regulation for the α1BAR subtype provides a model for studies of the differential regulation of the other α1AR subtypes and may lead to identification of new molecular targets for therapeutic intervention in a variety of disease states.

Original languageEnglish (US)
Pages (from-to)379-389
Number of pages11
JournalLife Sciences
Volume74
Issue number2-3
DOIs
StatePublished - Dec 5 2003

Fingerprint

Adrenergic alpha-1 Receptors
Adrenergic Receptors
Caveolae
Drug and Narcotic Control
Extracellular Signal-Regulated MAP Kinases
Physiology
Endocytosis
Protein Kinase C
Up-Regulation
Down-Regulation
Chemical activation
Modulation
Pharmacology
Therapeutics
Pharmaceutical Preparations

Keywords

  • Alpha-1 adrenergic receptor
  • Caveolae
  • Desensitization
  • Down-regulation
  • Endocytosis
  • Extracellular signal-regulated kinase
  • G protein coupling
  • Inherent instability
  • Internalization
  • Protein kinase C
  • Sequestration
  • Site-directed mutagenesis
  • Up-regulation

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Regulation of alpha-1B adrenergic receptor localization, trafficking, function, and stability. / Toews, Myron Lee; Prinster, Steven C.; Schulte, Nancy A.

In: Life Sciences, Vol. 74, No. 2-3, 05.12.2003, p. 379-389.

Research output: Contribution to journalArticle

Toews, Myron Lee ; Prinster, Steven C. ; Schulte, Nancy A. / Regulation of alpha-1B adrenergic receptor localization, trafficking, function, and stability. In: Life Sciences. 2003 ; Vol. 74, No. 2-3. pp. 379-389.
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