Developmentally regulated expression of ectonucleotidases NTPDase5 and NTPDase6 and UDP-responsive P2Y receptors in the rat cochlea |
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Authors: | Mary G O’Keeffe Peter R Thorne Gary D Housley Simon C Robson Srdjan M Vlajkovic |
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Institution: | (1) Department of Physiology, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand;(2) Discipline of Audiology, School of Population Health, Faculty of Medical and Health Sciences, The University of Auckland, Auckland, New Zealand;(3) Department of Physiology, School of Medical Sciences, University of New South Wales, Sydney, Australia;(4) Beth Israel Deaconess Medical Center, Harvard University, Boston, MA, USA; |
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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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