The role of taurine in mammalian hearing.
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Biomedical subjects
Publications and source records attributed to I S Kay.
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Experiments have been performed to investigate the ototoxic effects of sodium salicylate administration in anaesthetised rats as recorded by the auditory evoked brain-stem response (AEBR). Sodium salicylate (300 mg kg-1 i.p.) produced time-dependent increases in hearing threshold and decreases in the four principle peaks of the AEBR. Maximum responses were obtained at 4 h post-administration and were highly significant (P < 0.001). In a further series of experiments nimodipine, a calcium channel antagonist which has been suggested as a potential therapy for tinnitus, was administered at a dose of 2 mg kg-1 s.c. at the same time as sodium salicylate. This had no effect on the changes in hearing threshold. However, it did reduce the decrease in latencies of three of the four peaks of the AEBR, such that only the decrease in latency of the first peak was significantly different when compared to the pre-injection control latency (P < 0.01). We believe that these findings show specific neurophysiological correlates of salicylate ototoxicity. Since salicylate intoxication is used as the method for inducing tinnitus in animal models, the changes in the AEBR may provide an objective measure by which potential therapeutic intervention may be tested.
We have investigated the effects of the intravenous administration of 5-hydroxytryptamine upon the discharge frequency of pulmonary stretch receptors, irritant receptors and C fibres. Only C fibres were stimulated by this autacoid. MDL 72222 a selective 5-HT3 receptor antagonist blocks the C fibre stimulation by 5-hydroxytryptamine. It also blocks the C fibre response to miliary pulmonary embolism. These data confirm the hypothesis that 5-hydroxytryptamine is the humoral link between pulmonary embolism and tachypnoea.
Experiments have been performed to examine the effects of taurine supplementation on the ototoxicity of neomycin. It was found that concurrent administration of taurine and neomycin produced a greater degree of ototoxicity, as evidenced by increases in hearing thresholds, than with neomycin alone. The results are discussed in light of a recently proposed mechanism of aminoglycoside ototoxicity.
The pulmonary chemoreflexes evoked by phenylbiguanide (PBG), phenyldiguanide (PDG), phenylguanidine (PG) and 5-hydroxytryptamine (5-HT) have been investigated in the pentobarbitone-anaesthetized rabbit. The rank order of potency was 5-HT greater than PBG greater than PG greater than PDG. The responses evoked by all agonists were antagonized by pre-treatment with the selective 5-HT3 receptor antagonist MDL 72222, suggesting that their reflex effects are mediated by 5-HT3 receptors located on pulmonary vagal afferents. Furthermore, considering the low potency and long injection response time of PDG compared to PBG, we conclude that previous workers have used PBG and not PDG to identify non-myelinated pulmonary vagal afferents and to evoke the pulmonary chemoreflex.
The effect of the neuronal 5-HT3 receptor antagonist MDL 72222 has been investigated on the reflex tachypnoeic response to pulmonary embolism in pentobarbitone-anaesthetized rabbits. Pre-treatment with MDL 72222 (640 micrograms kg-1, 5 min prior to embolization) significantly attenuated the reflex tachypnoeic response associated with the injection of emboli. MDL 72222 had no effect on the bradycardia associated with embolization; however, it significantly reduced the decrease in arterial blood pressure and converted the decrease in tidal volume seen in pulmonary embolism to an increase. Furthermore, MDL 72222 had no effect on the decrease in circulating platelet count associated with embolization. The data suggest that 5-hydroxytryptamine is of primary importance in mediating the post-embolic increase in respiratory rate seen in this model of pulmonary embolism.
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