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

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 seven-membrane-spanning domain topography. The greatest sequence identity of this receptor protein is with the previously cloned hamster α(1B)-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 α(1B)-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 α(1B) receptor, results similar to pharmacologic binding properties described for the α(1A) receptor. Despite these similarities in pharmacological profiles, the bovine α₁-adrenergic receptor is sensitive to inhibition by the alkylating agent chloroethylclonidine unlike the α(1A)-adrenergic receptor subtype. In addition, a lack of expression in tissues where the α(1A) subtype exists suggests that this receptor may actually represent a novel α₁-adrenergic receptor subtype not previously appreciated by pharmacological criteria.