ATP antagonists cibacron blue, basilen blue and suramin alter sound-evoked responses of the cochlea and auditory nerve.
The P2-purinergic receptor antagonists suramin, cibacron blue and basilen blue, the latter two being isomers of reactive blue 2, were studied for their effects on sound-evoked responses from the cochlea (cochlear microphonic, CM; summating potential, SP; distortion product otoacoustic emissions, DPOAE) and auditory nerve (compound action potential, CAP). Local application of these compounds (10-1000 microM) into the cochlear perilymph was associated with concentration-dependent response alterations. Effects of suramin on cochlear responses were minimal: High-intensity SP was reduced slightly at concentrations > or = 330 microM without significant alterations in CM or DPOAEs. The amplitude of the auditory nerve CAP was suppressed and its latency increased at drug concentrations > or = 100 microM. Cibacron blue and basilen blue were of greater potency in their effects on cochlear and auditory nerve responses. DPOAEs were generally reduced, low-intensity SP was reduced and high-intensity SP was increased and CM was little affected at drug concentrations 100-1000 microM. The CAP was suppressed and its latency increased at concentrations > or = 33 microM. Effects of suramin were largely reversible; those associated with cibacron blue and basilen blue generally were not. To the extent that these drugs acted selectively as antagonists of ATP receptor-mediated activity, results support the hypothesis that endogenous ATP exerts profound actions at the level of the cochlea and the auditory nerve.
Kujawa
S G
SG
Kresge Hearing Research Laboratory of the South, Department of Otorhinolaryngology and Biocommunication, Louisiana State University Medical Center, New Orleans 70112.
Fallon
M
M
Bobbin
R P
RP
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors; D000818:Animals; D003051:Cochlea / Q000187:drug effects* / Q000502:physiology; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D004594:Electrophysiology; D005072:Evoked Potentials, Auditory / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D013237:Stereoisomerism; D013498:Suramin / Q000494:pharmacology; D014227:Triazines / Q000494:pharmacology; D000159:Vestibulocochlear Nerve / Q000187:drug effects* / Q000502:physiology
D004396:Coloring Agents; D011500:Protein Synthesis Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D014227:Triazines; C012842:Cibacron Blue F 3GA; D013498:Suramin; D000255:Adenosine Triphosphate