Adenosine is a modulator of hair cell-afferent neurotransmission

Adenosine has been implicated in neuromodulation in the central nervous system [(1985) Annu. Rev. Neurosci. 8, 103-124]. Its mechanism of action is thought to be a receptor-mediated inhibition of a transmitter release. To assess adenosine's role as a neuromodulator in the vestibular periphery, spontaneous activity of the afferent fibers in the ampullar nerve of the semicircular canal, in vitro, was used as the dependent variable. Afferent firing has been previously shown to depend on transmitter release by the hair cells [(1985) Brain Res. 330, 1-9]. Adenosine was shown to inhibit firing rate; the adenosine antagonist theophylline was shown to increase firing rate; the enzyme adenosine deaminase, which catabolizes adenosine to inosine, was shown to increase firing rate; the adenosine uptake inhibitor dipyridamole was shown to decrease firing rate; and adenosine was shown to be released from the isolated semicircular canal by electrical stimulation. All these findings are internally consistent and unreservedly support the hypothesis that adenosine has a neuromodulatory role in neurotransmission in the semicircular canal.