Previous studies indicate the presence of adenosine receptors in the c
ochlear tissues obtained from different animals. This study was initia
ted to determine the subtypes of adenosine receptor (AR) present in th
e chinchilla cochlea and to assess their function. Radioligand binding
studies demonstrate the presence of both the A(1)AR and A(3)AR in mem
branes prepared from the cochlea, using the radioligands [H-3]DPCPX an
d [I-125]APNEA. Estimates of the number (B-max) of A(1)AR and A(1)AR p
lus A(3)AR by saturation curves were 118 +/- 13 and 417 +/- 120 fmol/m
g, respectively, with the respective equilibrium dissociation constant
s (K-d) averaging 2.7 +/- 0.2 and 26.3 +/- 13.8 nM. No significant num
ber of A(2a)AR were detected using [H-3]CGS21680. The nonhydrolyzable
adenosine analog R-phenylisopropyladenosine (R-PIA, 1 mu M) elicited a
small but significant degree of inhibition of forskolin-stimulated ad
enylyl cyclase activity (10.4 +/- 2.5%) in cochlear membrane preparati
ons, which was insensitive to blockade by theophylline (100 mu M). Fur
thermore, R-PIA elicited an increase in inositol 1,4,5-trisphosphate p
roduction in dissociated cell preparations obtained from the cochlea.
No significant effect of R-PIA was observed on auditory measures such
as auditory brainstem evoked response, cochlear action potential and e
ndocochlear potential following round window application. However, rou
nd window application of R-PIA elicited significant increases in the a
ctivities of antioxidant enzymes such as superoxide dismutase and glut
athione peroxidase and significantly reduced the levels of malondialde
hyde, a marker of lipid peroxidation. These results suggest a potentia
l cytoprotective role of adenosine in the cochlea against oxidative da
mage.