Molecular cloning and expression of the cDNA for a novel α1-adrenergic receptor subtype

Debra A. Schwinn, Jon W. Lomasney, Wulfing Lorenz, Pamela J. Szklut, Robert T. Fremeau, Teresa L. Yang-Feng, Marc G. Caron, Robert J. Lefkowitz, Susanna Cotecchia

Research output: Contribution to journalArticlepeer-review

424 Scopus citations

Abstract

A novel α1-adrenergic receptor subtype has been cloned from a bovine brain cDNA library. The deduced amino acid sequence is that of a 466-residue polypeptide. The structure is similar to that of the other adrenergic receptors as well as the larger family of G protein-coupled receptors that have a presumed sevenmembrane-spanning domain topography. The greatest sequence identity of this receptor protein is with the previously cloned hamster α1B-adrenergic receptor being ≈72% within the presumed membrane-spanning domains. Localization on different human chromosomes provides evidence that the bovine cDNA is distinct from the hamster α1B-adrenergic receptor. The bovine cDNA clone expressed in COS7 cells revealed 10-fold higher affinity for the α1-adrenergic antagonists WB4101 and phentolamine and the agonist oxymetazoline as compared with the α1B receptor, results similar to pharmacologic binding properties described for the α1A receptor. Despite these similarities in pharmacological profiles, the bovine α1-adrenergic receptor is sensitive to inhibition by the alkylating agent chloroethylclonidine unlike the α1A-adrenergic receptor subtype. In addition, a lack of expression in tissues where the α1A subtype exists suggests that this receptor may actually represent a novel α1-adrenergic receptor subtype not previously appreciated by pharmacological criteria.

Original languageEnglish (US)
Pages (from-to)8183-8189
Number of pages7
JournalJournal of Biological Chemistry
Volume265
Issue number14
StatePublished - May 15 1990

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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