Kujawa S G, Glattke T J, Fallon M, Bobbin R P
Kresge Hearing Research Laboratory of the South, Department of Otorhinolaryngology and Biocommunication, Louisana State University Medical Center, New Orleans 70112-2234.
Hear Res. 1994 Apr;74(1-2):122-34. doi: 10.1016/0378-5955(94)90181-3.
The purpose of this investigation was to provide in vivo pharmacologic characterization of a cholinergic receptor mediating the suppressive effects of medial olivocochlear (MOC) efferent activation. MOC neurons were activated by contralateral sound and the resulting suppression of ipsilateral distortion product otoacoustic emissions (DPOAEs) was monitored before and after intracochlear perfusions of cholinergic antagonists. Results revealed a dose-dependent blockade of contralateral suppression of DPOAEs by a wide variety of nicotinic and muscarinic cholinergic receptor antagonists, as well as by non-traditional antagonists of cholinergic activity. The nicotinic antagonists, alpha-bungarotoxin, curare and kappa-bungarotoxin, and the glycine antagonist, strychnine, blocked contralateral suppression at nanomolar concentrations and demonstrated similar potencies. IC50 values were 2.38 x 10(-7), 2.79 x 10(-7), 3.81 x 10(-7) and 2.96 x 10(-7) M, respectively. These agents were followed in potency by the nicotinic antagonist, trimethaphan (1.75 x 10(-6) M), the M3 muscarinic antagonist, 4-DAMP (1.88 x 10(-6) M) and the GABAA antagonist, bicuculline (2.39 x 10(-6) M). Increasingly greater concentrations of the muscarinic antagonists, atropine (9.52 x 10(-6) M), AF-DX 116 (2.72 x 10(-5) M) and pirenzepine (8.24 x 10(-4) M) were necessary to block contralateral suppression of DPOAEs. The in vivo pharmacology of this putative outer hair cell cholinergic receptor suggests that it may be a member of the nicotinic family of receptors.
本研究的目的是对介导内侧橄榄耳蜗（MOC）传出神经激活抑制作用的胆碱能受体进行体内药理学特性分析。通过对侧声音激活MOC神经元，并在耳蜗内灌注胆碱能拮抗剂前后监测同侧畸变产物耳声发射（DPOAE）的抑制情况。结果显示，多种烟碱型和毒蕈碱型胆碱能受体拮抗剂以及胆碱能活性的非传统拮抗剂对DPOAE的对侧抑制具有剂量依赖性阻断作用。烟碱型拮抗剂α-银环蛇毒素、箭毒和κ-银环蛇毒素以及甘氨酸拮抗剂士的宁在纳摩尔浓度下阻断对侧抑制，并表现出相似的效力。IC50值分别为2.38×10⁻⁷、2.79×10⁻⁷、3.81×10⁻⁷和2.96×10⁻⁷M。这些药物之后依次是烟碱型拮抗剂三甲噻方（1.75×10⁻⁶M）、M3毒蕈碱型拮抗剂4-DAMP（1.88×10⁻⁶M）和GABAA拮抗剂荷包牡丹碱（2.39×10⁻⁶M）。需要越来越高浓度的毒蕈碱型拮抗剂阿托品（9.52×10⁻⁶M）、AF-DX Ⅰ16（2.72×10⁻⁵M）和哌仑西平（8.
