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Developmentally regulated expression of ectonucleotidases NTPDase5 and NTPDase6 and UDP-responsive P2Y receptors in the rat cochlea

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Abstract

Ectonucleoside triphosphate diphosphohydrolases (E-NTPDases) regulate complex extracellular P2 receptor signalling pathways in mammalian tissues by hydrolysing extracellular nucleotides to the respective nucleosides. All enzymes from this family (NTPDase1-8) are expressed in the adult rat cochlea. This study reports the changes in expression of NTPDase5 and NTPDase6 in the developing rat cochlea. These two intracellular members of the E-NTPDase family can be released in a soluble form and show preference for nucleoside 5′-diphosphates, such as UDP and GDP. Here, we demonstrate differential spatial and temporal patterns for NTPDase5 and NTPDase6 expression during cochlear development, which are indicative of both cytosolic and extracellular action via pyrimidines. NTPDase5 is noted during the early postnatal period in developing sensory hair cells and supporting Deiters’ cells of the organ of Corti, and primary auditory neurons located in the spiral ganglion. In contrast, NTPDase6 is confined to the embryonic and early postnatal hair cell bundles. NTPDase6 immunolocalisation in the developing cochlea underpins its putative role in hair cell bundle development, probably via cytosolic action, whilst NTPDase5 may have a broader extracellular role in the development of sensory and neural tissues in the rat cochlea. Both NTPDase5 and NTPDase6 colocalize with UDP-preferring P2Y4, P2Y6 and P2Y14 receptors during cochlear development, but this strong association was lost in the adult cochlea. Spatiotemporal topographic expression of NTPDase5 and NTPDase6 and P2Y receptors in adult and developing cochlear tissues provide strong support for the role of pyrimidinergic signalling in cochlear development.

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Acknowledgments

This study was supported by the Auckland Medical Research Foundation. MOK was also supported by the University of Auckland Doctoral Scholarship.

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Authors and Affiliations

  1. Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand

    Mary G. O’Keeffe, Peter R. Thorne, Gary D. Housley & Srdjan M. Vlajkovic

  2. Discipline of Audiology, School of Population Health, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand

    Peter R. Thorne

  3. Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, Australia

    Gary D. Housley

  4. Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA

    Simon C. Robson

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  1. Mary G. O’Keeffe
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  2. Peter R. Thorne
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  3. Gary D. Housley
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  4. Simon C. Robson
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  5. Srdjan M. Vlajkovic
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Correspondence to Srdjan M. Vlajkovic.

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O’Keeffe, M.G., Thorne, P.R., Housley, G.D. et al. Developmentally regulated expression of ectonucleotidases NTPDase5 and NTPDase6 and UDP-responsive P2Y receptors in the rat cochlea. Histochem Cell Biol 133, 425–436 (2010). https://doi.org/10.1007/s00418-010-0682-1

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