Ectonucleotidases and Purinoceptors in the Cochlea and Their Putative Role in Hearing

Abstract

It is well established that extracellular adenine nucleosides and nucleotides (adenosine, ATP and ADP) can influence cellular function in a range of tissues1. Interacting through specific receptors, termed purinoceptors, these compounds are known to act as neurotransmitters, neuromodulators, and humoral and trophic factors. Purinoceptors are classified into two main classes: P1 purinoceptors (subtypes A1, A2a, A2b and A3) which are preferentially responsive to adenosine and P2 purinoceptors (subtypes P2x and P2y) which are responsive to purine nucleotides (ATP, ADP, AMP)1. Over the past five years considerable evidence has emerged for a complex signalling role for extracellular purines in the inner ear2. Purinoceptors (P2x and P2y) have been identified in neural, sensory and secretory structures of the inner ear. Functional studies have shown a significant effect of extracellular ATP on inner ear function3, 4 and more recent studies have identified putative stores of ATP in secretory tissues. In addition, there is evidence for endogenous release of ATP into the fluids5 and for the presence of ectonucleotidases in cochlear tissues6. Our studies have been directed at identifying the functional role of extracellular ATP in the cochlea, that part of the inner ear which transduces sound into neural activity in the eighth cranial nerve (the auditory nerve). In this paper we summarise our current evidence on the nature and distribution of P2 purinoceptors, the storage and release of ATP and the extracellular hydrolysis of ATP in the cochlea. On the basis of this evidence we speculate on the significance of a neuromodulatory and humoral role for extracellular ATP in cochlear function and hence our sense of hearing.