Localization of β1-Adrenergic Receptors in the Cochlea and the Vestibular Labyrinth

Abstract

Sympathetic activation in a "fight or flight reaction" may put the sensory systems for hearing and balance into a state of heightened alert via β 1 -adrenergic receptors (β 1 -AR). The aim of the present study was to localize β 1 -AR in the gerbil inner ear by confocal immunocytochemistry, to characterize β 1 -AR by Western immunoblots, and to identify β 1 -AR pharmacologically by measurements of cAMP production. Staining for β 1 -AR was found in strial marginal cells, inner and outer hair cells, outer sulcus, and spiral ganglia cells of the cochlea, as well as in dark, transitional and supporting cells of the vestibular labyrinth. Receptors were characterized in microdissected inner ear tissue fractions as 55 kDa non-glycosylated species and as 160 kDa high-mannose-glycosylated complexes. Pharmacological studies using isoproterenol, ICI-118551 and CGP-20712A demonstrated β 1 -AR as the predominant adrenergic receptor in stria vascularis and organ of Corti. In conclusion, β 1 -AR are present and functional in inner ear epithelial cells that are involved in K + cycling and auditory transduction, as well as in neuronal cells that are involved in auditory transmission.

Supporting sensory transduction: cochlear fluid homeostasis and the endocochlear potential

“…It is thus not surprising that hearing is prepared for a successful ‘fight or flight reaction’. β 1 ‐Adrenergic receptors have been found in the organ of Corti, in the outer sulcus and in stria vascularis of the cochlea (Fauser et al 2004). Evidence is emerging that supports the concept that noradrenaline accelerates K + cycling in the cochlea and the vestibular labyrinth.…”

Postnatal developmental expression of the PDZ scaffolds Na+-H+ exchanger regulatory factors 1 and 2 in the rat cochlea

“…The rationale for the current study comes from the finding that the cochlea contains a number of proteins known to interact with NHERFs, plus numerous other proteins that have PDZ domains that could potentially interact with NHERFs. These cochlear proteins include NHE3 (Bond et al 1998), the ERM family (Kitajiri et al 2004), actin (Geal-Dor et al 1993;Nishida et al 1998), myosin (Boeda et al 2002;Johnson et al 2003;Mburu et al 2003;Kitajiri et al 2004;Belyantseva et al 2005;Kikkawa et al 2005), NBC3 (Bok et al 2003), P2Y1 (Teixeira et al 2000), β-adrenergic receptors (Fauser et al 2004), the vacuolar proton pump v-H + -ATPase (Stankovic et al 1997), Na + -K + ATPase (Ichimiya et al 1994;Erichsen et al 1996), growth factor receptors (Pickles and van Heumen 1997), glucocorticoid receptors (Erichsen et al 1996), TASK-1 background K + channels (Kanjhan et al 2004a), inwardly rectifying K + channels Kir1.1 (ROMK1) (Glowatzki et al 1995), Kir4.1 and Kir5.1 (Hibino et al 2004), aquaporin-4 (Mhatre et al 2002), glutamate transporter GLAST (Furness and Lehre 1997), and plasma membrane Ca 2+ -ATPase (Ichimiya et al 1994;Dumont et al 2001). …”

Immunohistochemical localization of adrenergic receptors in the rat organ of corti and spiral ganglion

“…Western blots for the human β 1 ‐AR at 51 kDa (NP_00675), very similar to rat β 1 ‐AR at 50.5 kDa (NP_036833), indicated apparent molecular masses of glycosylated proteins of 64 and 54 kDa (Dunigan et al, 2002). This antibody was used to analyze β 1 ‐AR protein expression in gerbil microdissected cochlear subfractions by Western blots (Fauser et al, 2004). The primary antibody for β 2 ‐AR was an affinity‐purified rabbit polyclonal raised against a synthetic peptide mapping at the C‐terminus of human β 2 ‐AR (1:500; Santa Cruz Biotechnology; sc‐569), cross‐reacting with rat sequence.…”

“…Adrenergic receptors are implicated in the regulation of K + secretion by marginal cells in the stria vascularis (Wangemann et al, 2000). Furthermore, evidence has been provided by Fauser et al (2004) that β 1 ‐AR is present within the organ of Corti.…”