EXPRESSION AND FUNCTION OF ADENOSINE RECEPTORS IN THE CHINCHILLA COCHLEA

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.