Noise induces A1 adenosine receptor expression in the chinchilla cochlea

Adenosine plays a major cytoprotective role during ischemia and conditions of oxidative stress. Previous studies in our laboratory indicate that oxidative stress induces expression of the A(1) adenosine receptor (A(1)AR) via activation of nuclear factor (NF)-kappaB. In this study, we tested whether noise exposure could induce oxidative stress and determine whether this induces expression of the A(1)AR in the chinchilla cochlea. Chinchillas were exposed to a 96 dB 4 kHz octave band of noise for 6 h of daily exposure, followed by an 18 h noise-free period. This noise paradigm resulted in threshold shifts of 10-60 dB over the frequency range (1-16 kHz) tested. Radioligand binding studies for the A(1)AR indicate a significant increase in receptor (similar to2-fold) expression soon after the first noise exposure period (usually within similar to8 h of the initiation of noise), which gradually returned to basal levels by day 7. The rise in A(1)AR levels was followed by a significant increase in malondialdehyde levels by day 3, which also recovered by day 7. Assessment of the activity of NADPH oxidase in the cochlea indicates a significant increase in enzyme activity which was evident by similar to8 h following initiation of noise exposure, and which persisted for at least up to day 3. Electrophoretic mobility shift assays indicate that the increase in A(1)AR was associated with a significant increase in NF-kappaB activity following noise exposure. We conclude that noise exposure induces A(1)AR expression, which might be mediated, in part, through generation of reactive oxygen species and activation of NF-kappaB. (C) 2003 Elsevier B.V. All rights reserved.