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.
All Science Journal Classification (ASJC) codes
- Sensory Systems