Molecular cloning and expression of the cDNA for a novel alpha 1-adrenergic receptor subtype.

Published

Journal Article

A novel alpha 1-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 seven-membrane-spanning domain topography. The greatest sequence identity of this receptor protein is with the previously cloned hamster alpha 1B-adrenergic receptor being approximately 72% within the presumed membrane-spanning domains. Localization on different human chromosomes provides evidence that the bovine cDNA is distinct from the hamster alpha 1B-adrenergic receptor. The bovine cDNA clone expressed in COS7 cells revealed 10-fold higher affinity for the alpha 1-adrenergic antagonists WB4101 and phentolamine and the agonist oxymetazoline as compared with the alpha 1B receptor, results similar to pharmacologic binding properties described for the alpha 1A receptor. Despite these similarities in pharmacological profiles, the bovine alpha 1-adrenergic receptor is sensitive to inhibition by the alkylating agent chloroethylclonidine unlike the alpha 1A-adrenergic receptor subtype. In addition, a lack of expression in tissues where the alpha 1A subtype exists suggests that this receptor may actually represent a novel alpha 1-adrenergic receptor subtype not previously appreciated by pharmacological criteria.

Full Text

Duke Authors

Cited Authors

  • Schwinn, DA; Lomasney, JW; Lorenz, W; Szklut, PJ; Fremeau, RT; Yang-Feng, TL; Caron, MG; Lefkowitz, RJ; Cotecchia, S

Published Date

  • May 15, 1990

Published In

Volume / Issue

  • 265 / 14

Start / End Page

  • 8183 - 8189

PubMed ID

  • 1970822

Pubmed Central ID

  • 1970822

International Standard Serial Number (ISSN)

  • 0021-9258

Language

  • eng

Conference Location

  • United States