Nitric Oxide in the Inner Ear with Particular Regard to Neurotansmission and Pharmacotherapy

Abstract: Research into nitric oxide (NO) in the inner ear has expanded explosively during recent years. There is evidence that NO is present in the various cochlear structures and its action is involved in physiological mechanisms, such as neurotransmission, and in pathological processes, e.g. ototoxicity. In order to obtain more data, sections of human cochlea were studied with immunostaining, using monoclonal antibodies to nitric oxide synthase (NOS) isoforms. Both constitutive NOS isoforms (I and III) were detected, but the predominant isoform was the neural type NOS I. Greatest affinity for NOS I was located in spiral ganglion (SG) cells and adjacent nerve fibres. The results imply that NO in the human cochlea could act as neurotransmitter. In the human inner ear, it has also been identified nicotinic acetylcholine receptors (n-ACh-r) by studying localization and distribution of α and β subunits. Both subunits were identified on SG cells, adjacent nerve fibres and in vestibular hair cells. It would appear that the subunits form an active complex at the level of these structures. Differences in the staining of β subunits at the level of the outer hair cells (OHC) suggest that different rows of OHCs could participate to different degrees in the function of n-ACh-r of the cochlea. The animal experiments were been designed to obtain information about NO involvement in the pathological mechanism of hearing impairment and to study the protection afforded by various drugs against damage to the inner ear associated with NO. The results of our investigations have demonstrated that NO produced by cNOS may mediate neurotoxicity in the inner ear early in the pathological process, whereas NO from inducible NOS may contribute by its cytotoxicity to the late phase of tissue damage in the inner ear. Analyses of the pharmacological effects of different drugs have shown that inhibitors of NO production and glutamate overproduction, as well as reactive oxygen species scavengers, could effectively protect the inner ear from injury caused by various pathological agents.