EFFECTS OF NEOMYCIN UPON TRANSMITTER RELEASE AND ACTION

Abstract

These experiments were designed to determine the site and mechanism of action of neomycin and streptomycin on cholinergic transmission. These agents depressed the response of rat diaphargm preparations to phrenic nerve stimulation and to injected acetylcholine (ACh); however, equi-effective neuromuscular blocking concentrations of neomycin (6 .times. 10-4 M), streptomycin (1.2 .times. 10-3 M) or d-tubocurarine (6.5 .times. 10-7 M) reduced the muscle response to injected ACh to 54, 27 and 15% of control, respectively, suggesting that neomycin and streptomycin have a presynaptic effect. This finding was confirmed by measuring ACh release from the diaphragm during phrenic nerve stimulation; neomycin (6 .times. 10-4 M) and streptomycin (1.2 .times. 10-4 M) depressed ACh release to 29 and 41% of control, respectively. In the cat superior cervical ganglion, neomycin (2 .times. 10-3 M) blocked ganglionic transmission, did not reduce the response of ganglion cells to injected nicotine and depressed ACh release during preganglionic nerve stimulation to 61% of control of normal Ca++ (2.5 mM) medium and to < 10% of control in low Ca++ (0.5 mM) medium. The increased accumulation of 45Ca induced in rat isolated ganglia by preganglionic nerve stimulation was not changed by d-tubocurarine (2 .times. 10-4 M), but was abolished by neomycin (2 .times. 10-3 M). Neomycin probably blocks ACh release by blocking the influx of Ca++ necessary for transmitter release. This conclusion suggested that neomycin should block noradrenaline [norepinephrine] release, and this was shown using the anococcygeus preparation from the rat. [Respiratory arrest has been associated with antibiotic therapy.].