A nicotinic-like receptor mediates suppression of distortion product otoacoustic emissions by contralateral sound.
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.
Kresge Hearing Research Laboratory of the South, Department of Otorhinolaryngology and Biocommunication, Louisana State University Medical Center, New Orleans 70112-2234.
S G
SG
Kujawa
T J
TJ
Glattke
M
M
Fallon
R P
RP
Bobbin
D000161:Acoustic Stimulation; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002038:Bungarotoxins / Q000494:pharmacology; D003051:Cochlea / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D003055:Cochlear Microphonic Potentials / Q000187:drug effects / Q000502:physiology; D004525:Efferent Pathways / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D018072:Hair Cells, Auditory, Outer / Q000502:physiology; D008297:Male; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D009847:Olivary Nucleus / Q000502:physiology; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000502:physiology; D011978:Receptors, Nicotinic / Q000502:physiology*; D013331:Strychnine / Q000494:pharmacology
D002038:Bungarotoxins; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D013331:Strychnine; D001640:Bicuculline