PPADS, an ATP antagonist, attenuates the effects of a moderately intense sound on cochlear mechanics.

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Bobbin RP

PPADS, an ATP antagonist, attenuates the effects of a moderately intense sound on cochlear mechanics.

Hear Res. 2001 Jun;156(1-2):10-6.

PubMed ID

11377878 [ View in PubMed

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Abstract

Increasing attention is being given to the role of neurotransmitters and other signaling substances in the damage induced by intense sound to the cochlea. Adenosine triphosphate (ATP) is one example of a putative neurotransmitter that may alter cochlear mechanics during sound exposure. The purpose of the present study was to test the hypothesis that endogenous extracellular ATP has a role in the generation of the changes in cochlear mechanics induced by moderate intense sound exposure. Guinea pigs were exposed to either: (1) a perilymphatic administration of pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 1 mM), an ATP antagonist; (2) a moderately intense sound (6 kHz tone, 95 dB SPL, 15 min); or (3) a combination of the PPADS and the sound. The effects on the cubic distortion product otoacoustic emissions (DPOAEs; 2f1-f2) were monitored using three sets of equal level primaries (f1=9.25 kHz, f2=10.8 kHz, 2f1-f2=7.7 kHz; f1=7.2 kHz, f2=8.4 kHz, 2f1-f2=6 kHz; f1=5.55 kHz, f2=6.5 kHz, 2f1-f2=4.6 kHz). PPADS alone had no effect on the cubic DPOAEs monitored. The intense sound alone suppressed all three cubic DPOAEs. The combination of PPADS with the intense sound induced a suppression of the cubic DPOAEs that was equal to or greater than induced by the intense sound alone at f2=10.8 kHz but was equal to or less than induced by the intense sound at f2=8.4 and 6.5 kHz. After washing the PPADS out of the cochlea with artificial perilymph, all three cubic DPOAEs were suppressed less in the PPADS with intense sound treatment group than in the intense sound alone group. The PPADS appeared to provide protection from the intense sound. Results are consistent with the hypothesis that extracellular ATP is involved in the changes in cochlear mechanics induced by moderately intense sound exposure.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Pyridoxal phosphate	Sphingosine-1-phosphate lyase 1	Protein	Humans	Unknown	Cofactor	Details