Molecular and pharmacological characteristics of the gerbil α1a-adrenergic receptor

Abstract

The spiral modiolar artery supplies blood and essential nutrients to the cochlea. Our previous functional study indicates the α1A–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 α1a-adrenergic receptor have not been determined. Thus we cloned, expressed and characterized the gerbil α1a-adrenergic receptor and then compared its molecular and pharmacological properties to those of other mammalian α1a-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 α1a-receptors, respectively. We transiently transfected the α1a-adrenergic receptor into COS-1 cells and determined its pharmacological characteristics by [3H]prazosin binding. Unlabeled prazosin had a Ki of 0.89 ± 0.1 nM. The α1A-adrenergic receptor-selective antagonists, 5-methylurapidil and WB-4101, bound with high affinity and had Ki values of 4.9 ± 1 and 1.0 ± 0.1 nM, respectively. BMY-7378, an α1D-adrenergic receptor-selective antagonist, bound with low affinity (260 ± 60 nM). The 91.6% amino acid sequence identity and Kis of the cloned gerbil α1a-adrenergic receptor are similar to those of the human α1a-adrenergic receptor clone. These results show that the gerbil α1a-adrenergic receptor is representative of the human α1a-adrenergic receptor, lending validity to the use of the gerbil spiral modiolar artery as a model in studies of vascular disorders of the cochlea.

β1- and β2-adrenergic stimulation-induced electrogenic transport by human endolymphatic sac epithelium and its clinical implications

“…Adrenergic stimulation is believed to be involved in the regulation of microvascular tone, ion homeostasis, endolymphatic pressure, and autonomic nervous system function in the inner ear 11 15 22 23 . Various α- and β- adrenergic receptors have been proven to be distributed in the epithelial cells, vessels, and ganglions in the whole inner ear organs, and the receptors in the epithelial cells of the inner ear are assumed to be involved mainly in the regulation of ion transport activities.…”