title: Molecular and pharmacological characteristics of the gerbil α(1a)-adrenergic receptor.
abstract: The spiral modiolar artery supplies blood and essential nutrients to the cochlea. Our previous functional study indicates the α(1A)-adrenergic receptor subtype mediates vasoconstriction of the gerbil spiral modiolar artery. Although the gerbil cochlea is often used as a model in hearing research, the molecular and pharmacological characteristics of the cloned gerbil α(1a)-adrenergic receptor have not been determined. Thus we cloned, expressed and characterized the gerbil α(1a)-adrenergic receptor and then compared its molecular and pharmacological properties to those of other mammalian α(1a)-adrenergic receptors. The cDNA clone contained 1404 nucleotides, which encoded a 467 amino acid peptide with a deduced sequence having 96.8, 96.4 and 91.6% identity to rat, mouse and human α(1a)-receptors, respectively. We transiently transfected the α(1a)-adrenergic receptor into COS-1 cells and determined its pharmacological characteristics by [(3)H]prazosin binding. Unlabeled prazosin had a K(i) of 0.89±0.1nM. The α(1A)-adrenergic receptor-selective antagonists, 5-methylurapidil and WB-4101, bound with high affinity and had K(i) values of 4.9±1 and 1.0±0.1nM, respectively. BMY-7378, an α(1D)-adrenergic receptor-selective antagonist, bound with low affinity (260±60nM). The 91.6% amino acid sequence identity and K(i)s of the cloned gerbil α(1a)-adrenergic receptor are similar to those of the human α(1a)-adrenergic receptor clone. These results show that the gerbil α(1a)-adrenergic receptor is representative of the human α(1a)-adrenergic receptor, lending validity to the use of the gerbil spiral modiolar artery as a model in studies of vascular disorders of the cochlea.
authors.affiliation: Department of Pharmacology, Creighton University, 2500 California Plaza, Omaha, NE 68178, USA. kellymwitt@hotmail.com
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Witt
authors.forename: Charles S
authors.initials: CS
authors.lastname: Bockman
authors.forename: Herbert K
authors.initials: HK
authors.lastname: Dang
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Gruber
authors.forename: Philine
authors.initials: P
authors.lastname: Wangemann
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Scofield
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000378:metabolism* / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001158:Arteries / Q000187:drug effects / Q000378:metabolism; D019556:COS Cells; D002522:Chlorocebus aethiops; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D003001:Cloning, Molecular; D003051:Cochlea / Q000098:blood supply*; D017124:Conserved Sequence; D004146:Dioxanes / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005849:Gerbillinae; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D010879:Piperazines / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D020539:Sequence Analysis, Protein; D014162:Transfection; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: C547713:ADRA1A protein, human; C547714:Adra1a protein, mouse; C547715:Adra1a protein, rat; D058668:Adrenergic alpha-1 Receptor Antagonists; D004146:Dioxanes; D010879:Piperazines; D018340:Receptors, Adrenergic, alpha-1; C057446:5-methylurapidil; C051731:chlorethylclonidine; C010654:(2-(2',6'-dimethoxy)phenoxyethylamino)methylbenzo-1,4-dioxane; C053428:BMY 7378; D003000:Clonidine; D011224:Prazosin
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