Inhibition of Release of Acetylcholine by Strychnine and its Implications regarding Transmission by the Olivo-cochlear Bundle

Abstract

IN previous experiments, we have investigated the effects of various cholinergic blocking agents and other drugs on the release of acetylcholine (ACh) from the Ringer–Locke perfused superior cervical ganglion of the cat after injection of carbachol (0.5–1.0 (µg) into the perfusion solution or supramaximal electrical stimulation (10 c/s for 3 min) of the preganglionic trunk (ref. 1 and our work in preparation). Hexamethonium (10⁻⁴ molar), which does not block the release of ACh by preganglionic stimulation^2,3, markedly reduced release of ACh induced by carbachol. Similarly, atropine sulphate (10–33 µg) consistently, and 3 × 10⁻⁵ molar diallyl bisnortoxiferine or 3 × 10⁻⁴ molar dihydro-β-erythroidine occasionally, reduced the amount of ACh released by carbachol, but not by preganglionic stimulation; 2 × 10⁻⁴ molar mecamylamine did not affect release of ACh with either type of stimulus. Procaine, at 50 or 10 (µg/ml., reduced release of ACh which had been induced by either preganglionic stimulation or carbachol, but at 1 µg/ml, it was effective only against carbachol-induced release of ACh. Of all the drugs tested, only strychnine blocked or reduced selectively the release of ACh induced by preganglionic stimulation, an effect that was statistically significant (P < 0.05) for the dosage range of 100–1.0 µg/ml.; carbachol-induced release of ACh was reduced markedly at a concentration of 100 µg/ml., but inconsistently or not at all at concentrations of 31.6 µg/ml. or lower¹. Strychnine in concentrations of 10⁻⁶–10⁻⁵ g/ml. has been shown to reduce the output of ACh by the ileum of guinea-pig after coaxial stimulation or treatment with various drugs⁴. The inhibition by strychnine of the release of ACh by nerve impulse suggests a possible explanation for the apparent inconsistency between histochemical and pharmacological findings at the terminals of the olivo-cochlear bundle of Rasmussen.