PPADS, an ATP antagonist, attenuates the effects of a moderately intense sound on cochlear mechanics.
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.
Bobbin
R P
RP
Kresge Hearing Research Laboratory of the South, Department of Otorhinolaryngology and Biocommunication, Louisiana State University Medical Center, 533 Bolivar Street, 5th floor, New Orleans, LA 70112-2234, USA. rbobbi@lsuhsc.edu
D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors*; D000818:Animals; D003051:Cochlea / Q000187:drug effects / Q000502:physiology; D006168:Guinea Pigs; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D010469:Perceptual Distortion / Q000502:physiology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D013016:Sound
C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D000255:Adenosine Triphosphate