title: Role of adenosine kinase in cochlear development and response to noise.
abstract: Adenosine signalling has an important role in cochlear protection from oxidative stress. In most tissues, intracellular adenosine kinase (ADK) is the primary route of adenosine metabolism and the key regulator of intracellular and extracellular adenosine levels. The present study provides the first evidence for ADK distribution in the adult and developing rat cochlea. In the adult cochlea, ADK was localized to the nuclear or perinuclear region of spiral ganglion neurons, lateral wall tissues, and epithelial cells lining scala media. In the developing cochlea, ADK was strongly expressed in multiple cell types at birth and reached its peak level of expression at postnatal day 21 (P21). Ontogenetic changes in ADK expression were evident in the spiral ganglion, organ of Corti, and stria vascularis. In the spiral ganglion, ADK showed a shift from predominantly satellite cell immunolabelling at P1 to neuronal expression from P14 onward. In contrast to the role of ADK in various aspects of cochlear development, the ADK contribution to the cochlear response to noise stress was less obvious. Transcript and protein levels of ADK were unaltered in the cochlea exposed to broadband noise (90-110 dBSPL, 24 hr), and the selective inhibition of ADK in the cochlea with ABT-702 failed to restore hearing thresholds after exposure to traumatic noise. This study indicates that ADK is involved in purine salvage pathways for nucleotide synthesis in the adult cochlea, but its role in the regulation of adenosine signalling under physiological and pathological conditions has yet to be established.
authors.affiliation: Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Aukland, New Zealand. s.vlajkovic@auckland.ac.nz
authors.forename: Srdjan M
authors.initials: SM
authors.lastname: Vlajkovic
authors.forename: Cindy X
authors.initials: CX
authors.lastname: Guo
authors.forename: Nuwan
authors.initials: N
authors.lastname: Dharmawardana
authors.forename: Ann Chi Yan
authors.initials: AC
authors.lastname: Wong
authors.forename: Detlev
authors.initials: D
authors.lastname: Boison
authors.forename: Gary D
authors.initials: GD
authors.lastname: Housley
authors.forename: Peter R
authors.initials: PR
authors.lastname: Thorne
mesh_terms: D000248:Adenosine Kinase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D003051:Cochlea / Q000166:cytology / Q000201:enzymology* / Q000254:growth & development*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D006317:Hearing Loss, Noise-Induced / Q000201:enzymology* / Q000503:physiopathology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009622:Noise / Q000009:adverse effects*; D009711:Nucleotides / Q000096:biosynthesis; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D009025:Morpholines; D009711:Nucleotides; D011743:Pyrimidines; C416933:ABT 702; D000248:Adenosine Kinase