Molecular and pharmacological characteristics of the gerbil α 1a-adrenergic receptor

Kelly M. Witt, Charles Bockman, Herbert K. Dang, Daniel D. Gruber, Philine Wangemann, Margaret A. Scofield

Research output: Contribution to journalArticle

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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 [ 3H]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 is 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.

Original languageEnglish
Pages (from-to)144-150
Number of pages7
JournalHearing Research
Volume283
Issue number1-2
DOIs
StatePublished - Jan 2012

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Gerbillinae
Adrenergic Receptors
Pharmacology
Cochlea
Adrenergic Antagonists
Arteries
Prazosin
Clone Cells
COS Cells
Vasoconstriction
Hearing
Blood Vessels
Amino Acid Sequence
Nucleotides
Complementary DNA
Amino Acids
Food
Peptides

All Science Journal Classification (ASJC) codes

  • Sensory Systems

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Molecular and pharmacological characteristics of the gerbil α 1a-adrenergic receptor. / Witt, Kelly M.; Bockman, Charles; Dang, Herbert K.; Gruber, Daniel D.; Wangemann, Philine; Scofield, Margaret A.

In: Hearing Research, Vol. 283, No. 1-2, 01.2012, p. 144-150.

Research output: Contribution to journalArticle

Witt, Kelly M. ; Bockman, Charles ; Dang, Herbert K. ; Gruber, Daniel D. ; Wangemann, Philine ; Scofield, Margaret A. / Molecular and pharmacological characteristics of the gerbil α 1a-adrenergic receptor. In: Hearing Research. 2012 ; Vol. 283, No. 1-2. pp. 144-150.
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