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GEOFFREY BURNSTOCK AN. R. ACAD. NAC. FARM.
during the development of the cataract and opacification; disulfirom
and aminoguanidine, which inhibit inducible NO and scavenge
reactive oxygen species, attenuate the decrease in ATP, resulting in
a delay in cataract development.
Ear
In the auditory system ATP, acting via P2Y receptors, depresses
sound-evoked gross compound action potentials in the auditory nerve
and the distortion product otoacoustic emission, the latter being a
measure of the active process of the outer hair cells (38). P2X splice
variants are found on the endolymphatic surface of the cochlear
endothelium, an area associated with sound transduction. Both P2X
and P2Y receptors have been identified in the vestibular system. ATP
may regulate fluid homeostasis, cochlear blood flow, hearing
sensitivity and development, and thus may be useful in the treatment
of Ménières disease, tinnitus and sensorineural deafness.
Excessive noise can irreversibly damage hair cell stereocilia
leading to deafness. Data has been presented that release of ATP from
damaged hair cells is required for Ca2+ wave propagation through the
support cells of the organ of Corti, involving P2Y receptors, and this
may constitute the fundamental mechanism to signal the occurrence
of hair cell damage. ATP is claimed to mitigate the effects of noise
trauma, although the primary mechanisms involved are not clear.
Nasal organ
Purinergic receptors have been described in the nasal mucosa,
including the expression of P2X3 receptors on olfactory neurones (39).
Enhanced sensitivity to odours in the presence of P2 purinergic
antagonists suggests that low-level endogenous ATP normally reduces
odour responsiveness. It appears that the induction of heat-shock
proteins by noxious odour damage can be prevented by the in vivo
administration of P2 receptor antagonists. The predominantly
suppressive effect of ATP in odour responses could play a role in the
reduced odour sensitivity that occurs during acute exposure to
noxious fumes and may be a novel neuroprotective mechanism.
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