Elsevier

Hearing Research

Volume 105, Issues 1–2, March 1997, Pages 130-140
Hearing Research

Expression and function of adenosine receptors in the chinchilla cochlea

https://doi.org/10.1016/S0378-5955(96)00204-3Get rights and content

Abstract

Previous studies indicate the presence of adenosine receptors in the cochlear tissues obtained from different animals. This study was initiated to determine the subtypes of adenosine receptor (AR) present in the chinchilla cochlea and to assess their function. Radioligand binding studies demonstrate the presence of both the A1 AR and A3AR in membranes prepared from the cochlea, using the radioligands [3H]DPCPX and [125I]APNEA. Estimates of the number (Bmax) of A1AR and A1AR plus A3AR by saturation curves were 118 ± 13 and 417 ± 120 fmol/mg, respectively, with the respective equilibrium dissociation constants (Kd) averaging 2.7 ± 0.2 and 26.3 ± 13.8 nM. No significant number of A2aAR were detected using [3H]CGS21680. The nonhydrolyzable adenosine analog R-phenylisopropyladenosine (R-PIA, 1 μM) elicited a small but significant degree of inhibition of forskolin-stimulated adenylyl cyclase activity (10.4 ± 2.5%) in cochlear membrane preparations, which was insensitive to blockade by theophylline (100 μM). Furthermore, R-PIA elicited an increase in inositol 1,4,5-trisphosphate production 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 endocochlear potential following round window application. However, round window application of R-PIA elicited significant increases in the activities of antioxidant enzymes such as superoxide dismutase and glutathione peroxidase and significantly reduced the levels of malondialdehyde, a marker of lipid peroxidation. These results suggest a potential cytoprotective role of adenosine in the cochlea against oxidative damage.

Reference (56)

  • MaggirwarS.B. et al.

    Adenosine acts as an endogenous activator of the cellular antioxidant defense system

    Biochem. Biophys. Res. Commun.

    (1994)
  • MisraH.P. et al.

    The role of superoxide anion in the autooxidation of epinephrine and a sample assay for super-oxide dismutase

    J. Biol. Chem.

    (1972)
  • Mun˜ozD.J.B. et al.

    Extracellular adenosine 5′-triphosphate (ATP) in the endolymphatic compartment influences cochlear function

    Hear. Res.

    (1995)
  • OgawaK. et al.

    G proteins coupled to phosphoinasitide hydrolysis in the cochlear and vestibular sensory epithelia of the rat are insensitive to cholera and pertussis toxins

    Hear. Res.

    (1994)
  • OhkawaH. et al.

    Reaction of linoleic acid hydroperoxide with thiobarbituric acid

    J. Lipid Res.

    (1978)
  • ParsonsW.J. et al.

    Heterologous densensitization of the inhibitory A1 adenosine receptor-adenylate cyclase system in rat adipocytes. Regulation of both Ns and Ni

    J. Biol. Chem.

    (1987)
  • PiersonM.G. et al.

    Superoxide dismutase activity in the cochlea

    Hear. Res.

    (1982)
  • RamkumarV. et al.

    The A3 adenosine receptor is the unique adenosine receptor which facilitates release of allergic mediators in mast cells

    J. Biol. Chem.

    (1993)
  • RybakL.P. et al.

    Mechanism of protection by diethyldithiocarbamate against cisplatin ototoxicity: antioxidant system

    Fundament. Appl. Toxicol.

    (1995)
  • SalomonY. et al.

    A highly sensitive adenylate cyclase assay

    Anal. Biochem.

    (1974)
  • SchachtJ.

    Adenylyl cyclase and cochlear fluid balance

    Am. J. Otolaryngol.

    (1982)
  • ZuninoF. et al.

    Protective effect of reduced glutathione against cisplatin-induced renal and systemic toxicity and its influence on the therapeutic activity of antitumor drug

    Chem. Biol. Interact.

    (1989)
  • AebiN.

    Catalase, in vitro

    Methods Enzymol.

    (1984)
  • AhlstromP. et al.

    Cyclic AMP and adenylate cyclase in the inner ear

    Laryngoscope

    (1975)
  • AshmoreJ.F. et al.

    Control of intracellular calcium by ATP in isolated outer hair cells of the guinea-pig cochlea

    J. Physiol.

    (1990)
  • BilletT.E. et al.

    The nature and progression of injury in the organ of Corti during ischemia

    Hear. Res.

    (1989)
  • BurnstockG.

    A basis for distinguishing two types of purinergic receptors

  • DelahauntyT. et al.

    Regulation of GH3 cell function via A1 receptor

    Biochem. J.

    (1988)
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