Molecular cloning and expression of the cDNA for the α(1A)-adrenergic receptor: The gene for which is located on human chromosome 5

Jon W. Lomasney*, Susanna Cotecchia, Wulfing Lorenz, Wah Ying Leung, Debra A. Schwinn, Teresa L. Yang-Feng, Michael Brownstein, Robert J. Lefkowitz, Marc G. Caron

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

378 Scopus citations

Abstract

Pharmacological and molecular cloning studies have demonstrated heterogeneity of α1-adrenergic receptors. We have now cloned two α1-adrenergic receptors from a rat cerebral cortex cDNA library, using the hamster α(1B)-adrenergic receptor as a probe. The deduced amino acid sequence of clone RA42 encodes a protein of 560 amino acids whose putative topology is similar to that of the family of G-protein-coupled receptors. The primary structure though most closely resembles that of an α1-adrenergic receptor, having approximately 73% amino acid identity in the putative transmembrane domains with the previously isolated hamster α(1B) receptor. Analysis of the ligand binding properties of RA42 expressed in COS-7 cells with a variety of adrenergic ligands demonstrates a unique α1-adrenergic receptor pharmacology. High affinity for the antagonist WB4101 and agonists phenylephrine and methoxamine suggests that cDNA RA42 encodes the α(1A) receptor subtype. Northern blot analysis of various rat tissues also shows the distribution expected of the α(1A) receptor subtype with abundant expression in vas deferens followed by hippocampus, cerebral cortex, aorta, brainstem, heart and spleen. The second α1-adrenergic receptor cloned represents the rat homolog of the hamster α(1B) subtype. Expression of mRNA for this receptor is strongly detected in liver followed by heart, cerebral cortex, brain stem, kidney, lung, and spleen. This study provides definitive evidence for the existence of three α1-adrenergic receptor subtypes.

Original languageEnglish (US)
Pages (from-to)6365-6369
Number of pages5
JournalJournal of Biological Chemistry
Volume266
Issue number10
StatePublished - 1991

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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