Distribution of NTPDase5 and NTPDase6 and the regulation of P2Y receptor signalling in the rat cochlea

O’Keeffe, Mary G.; Thorne, Peter R.; Housley, Gary D.; Robson, Simon C.; Vlajkovic, Srdjan M.

doi:10.1007/s11302-010-9190-y

Cited by 15 publications

(13 citation statements)

References 49 publications

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“…The increase in expression of purinergic signalling with the lower levels of noise may reflect a physiological and protective adaptation which may be suppressed with tissue injury that would occur with the higher level exposures. A similar exposure dependence occurs with both NTPDase [50] and P2X 7 (unpublished observation) upregulation. The fact that P2X 2 R upregulation with noise exposure is very much reduced in older animals suggests an age-dependent pattern of purinergic response to noise stress.…”

Section: Discussionsupporting

confidence: 62%

“…ATP-gated ion channels composed of P2X 2 subunits have been identified in the epithelial cells of Reissner's membrane [17], which separates the endolymph of the scala media from the perilymph of the scala vestibuli, the stereocilia and surface of the hair cells, and the surface of supporting cells of the organ of Corti [48]. Recovery of the response to exogenous ATP is due to the rapid metabolism of ATP by ectonucleotidases (NTPDases) [49][50][51]. The change in CoPR relative to the change in EP was smaller in mice compared with that observed in guinea pigs [5].…”

Section: Discussionmentioning

confidence: 99%

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Reduced P2x2 receptor-mediated regulation of endocochlear potential in the ageing mouse cochlea

Telang

Paramananthasivam

Vlajkovic

et al. 2010

Purinergic Signalling

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Extracellular adenosine triphosphate (ATP) has profound effects on the cochlea, including an effect on the regulation of the endocochlear potential (EP). Noise-induced release of ATP into the endolymph activates a shunt conductance mediated by P2X 2 receptors in tissues lining the endolymphatic compartment, which reduces the EP and, consequentially, hearing sensitivity. This may be a mechanism of adaptation or protection from high sound levels. As inaction of such a process could contribute to hearing loss, this study examined whether the action of ATP on EP changes with age and noise exposure in the mouse. The EP and the endolymphatic compartment resistance (CoPR) were measured in mice (CBA/CaJ) aged between 3 and 15 months. The EP and CoPR declined slightly with age with an associated small, but significant, reduction in auditory brainstem response thresholds. ATP (100-1,000 μM) microinjected into the endolymphatic compartment caused a dosedependent decline in EP correlated to a similar decrease in CoPR. This was blocked by pyridoxal-phosphate-6-azophenyl-2′,4′-disulfonate, consistent with a P2X 2 receptormediated shunt conductance. There was no substantial difference in the ATP response with age. Noise exposure (octave-band noise 80-100 decibels sound pressure level (dBSPL), 48 h) in young animals induced an upregulation of the P2X 2 receptor expression in the organ of Corti and spiral limbus, most noticeably with the 90-dB exposure. This did not occur in the aged animals except following exposure at 90 dBSPL. The EP response to ATP was muted in the noiseexposed aged animals except following the 90-dB exposure. These findings provide some evidence that the adaptive response of the cochlea to noise may be reduced in older animals, and it is speculated that this could increase their susceptibility to noise-induced injury.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Reduced P2x2 receptor-mediated regulation of endocochlear potential in the ageing mouse cochlea

Telang

Paramananthasivam

Vlajkovic

et al. 2010

Purinergic Signalling

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“…These “prone-to-bend” areas were especially evident in 3 rd row DC at the basal region of the cochlea, whose lower limbs bent towards the tunnel of Corti, and in 1 st row DC at the apical region of the cochlea, whose lower limbs bent away the tunnel of Corti. Interestingly, many images of the organ of Corti available in the literature —from different species and obtained with different techniques— show similar “twisted” DCs’ lower limbs (see, for example, (Hardie et al, 2004; Huang et al, 2010; O'Keeffe et al, 2010; Shim, 2011)). Moreover, a beautiful drawing by Retzius (Plate XXV, Figs.…”

Section: Discussionmentioning

confidence: 99%

Deiters cells tread a narrow path—The Deiters cells-basilar membrane junction—

2012

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Deiters cells extend from the basilar membrane to the reticular lamina and, together with pillar cells and outer hair cells, structurally define the micro-architecture of the organ of Corti. Studying vibrotome sections of the mouse organ of Corti with confocal and scanning electron microscopy we found that the basal pole of every Deiters cell, independently of their position in the organ of Corti and along the cochlear spiral, attached to the basilar membrane within a 15.1±0.3 µm-wide stripe running the length of the cochlear spiral adjacent to the row of outer pillar cells. All Deiters cells’ basal poles had similar diameter and general morphology, and distributed on the stripe in a precise arrangement with a center-to-center distance of 7.1±0.3 µm between neighbor cells of the same row and 5.9±0.4 µm for neighbor cells in adjacent rows. Complete detachment of Deiters cells revealed an elliptical imprint on the top surface of the basilar membrane consisting of a smaller central structure with a very smooth surface surrounded by a rougher area, suggesting the presence of two different anchoring junctions. These previously unidentified morphological features of Deiters cells could be critical for the mechanical response of the organ of Corti.

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“…Furthermore, recent evidence suggests that montelukast possesses a range of secondary activities independent of CysLTR1, including inhibition of 5-LO, histone acetyltransferase, cAMP phosphodiesterase, and interference with purinergic P2Y receptors (38)(39)(40). In particular, P2Y receptors have been reported to be linked to NIHL; P2Y receptors are widely expressed in the cochlear tissue and play a role in the maintenance of K + transport and cycling (41). In addition, acoustic overstimulation induces ATP release (42) and upregulates the expression of P2Y6 and P2Y14 receptors in the cochlea (41).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, P2Y receptors have been reported to be linked to NIHL; P2Y receptors are widely expressed in the cochlear tissue and play a role in the maintenance of K + transport and cycling (41). In addition, acoustic overstimulation induces ATP release (42) and upregulates the expression of P2Y6 and P2Y14 receptors in the cochlea (41). P2Y receptors have also been known to be involved in the propagation and sensing of noise damage (43).…”

Section: Discussionmentioning

confidence: 99%

Role of cysteinyl leukotriene signaling in a mouse model of noise-induced cochlear injury

Park¹,

Kang²,

Seo

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Noise-induced hearing loss is one of the most common types of sensorineural hearing loss. In this study, we examined the expression and localization of leukotriene receptors and their respective changes in the cochlea after hazardous noise exposure. We found that the expression of cysteinyl leukotriene type 1 receptor (CysLTR1) was increased until 3 d after noise exposure and enhanced CysLTR1 expression was mainly observed in the spiral ligament and the organ of Corti. Expression of 5-lipoxygenase was increased similar to that of CysLTR1, and there was an accompanying elevation of CysLT concentration. Posttreatment with leukotriene receptor antagonist (LTRA), montelukast, for 4 consecutive days after noise exposure significantly decreased the permanent threshold shift and also reduced the hair cell death in the cochlea. Using RNA-sequencing, we found that the expression of matrix metalloproteinase-3 (MMP-3) was up-regulated after noise exposure, and it was significantly inhibited by montelukast. Posttreatment with a MMP-3 inhibitor also protected the hair cells and reduced the permanent threshold shift. These findings suggest that acoustic injury up-regulated CysLT signaling in the cochlea and cochlear injury could be attenuated by LTRA through regulation of MMP-3 expression. This study provides mechanistic insights into the role of CysLTs signaling in noise-induced hearing loss and the therapeutic benefit of LTRA.

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Distribution of NTPDase5 and NTPDase6 and the regulation of P2Y receptor signalling in the rat cochlea

Cited by 15 publications

References 49 publications

Reduced P2x2 receptor-mediated regulation of endocochlear potential in the ageing mouse cochlea

Reduced P2x2 receptor-mediated regulation of endocochlear potential in the ageing mouse cochlea

Deiters cells tread a narrow path—The Deiters cells-basilar membrane junction—

Role of cysteinyl leukotriene signaling in a mouse model of noise-induced cochlear injury

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