Kujawa S G, Fallon M, Bobbin R P
Kresge Hearing Research Laboratory of the South, Department of Otorhinolaryngology and Biocommunication, Louisiana State University Medical Center, New Orleans 70112.
Hear Res. 1994 Aug;78(2):181-8. doi: 10.1016/0378-5955(94)90024-8.
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.
研究了P2-嘌呤能受体拮抗剂苏拉明、汽巴克隆蓝和碱性蓝(后两者是活性蓝2的异构体)对耳蜗声音诱发反应(耳蜗微音电位,CM;总和电位,SP;畸变产物耳声发射,DPOAE)和听神经(复合动作电位,CAP)的影响。将这些化合物(10-1000微摩尔)局部应用于耳蜗外淋巴与浓度依赖性反应改变有关。苏拉明对耳蜗反应的影响最小:在浓度≥330微摩尔时,高强度SP略有降低,而CM或DPOAE无明显改变。在药物浓度≥100微摩尔时,听神经CAP的幅度受到抑制,潜伏期延长。汽巴克隆蓝和碱性蓝对耳蜗和听神经反应的作用更强。在药物浓度为100-1000微摩尔时,DPOAE通常降低,低强度SP降低,高强度SP升高,CM几乎不受影响。在浓度≥33微摩尔时,CAP受到抑制,潜伏期延长。苏拉明的作用在很大程度上是可逆的;与汽巴克隆蓝和碱性蓝相关的作用通常不可逆。就这些药物选择性地作为ATP受体介导活性的拮抗剂而言,结果支持内源性ATP在耳蜗和听神经水平发挥深远作用的假说。