Effects of 1-Methyl-5-Chloroindoline Methylbromide (S-6) on Renshaw Cells of Cats

Abstract

Abstract-Effects of 1-methyl-5-chloroindoline methylbromide (S-6) on Renshaw cells were investigated in cats anesthetized with pentobarbital sodium. S-6 proved to have little effect on spike discharges of Renshaw cells when administered intra venously, but the agent electrophoretically applied revealed excitatory effects which resembled the action of methacholine and such effects were blocked by intravenous administration of atropine. It was concluded that (1) S-6 is impermeant to the blood brain barrier and (2) the excitatory action of S-6 on Renshaw cells is muscarinic in nature.Previous reports from this laboratory have demonstrated that 1-methyl-5-chloroindoline methylbromide (S-6) exerts a remarkable parasympathomimetic effect on various peripheral organs (1, 2), and that i.v. administration revealed little effect on activities of the central nervous system, such as EEG, spinal reflexes and anti-convulsive activity (3). These results suggested that intravenously administered S-6 may not enter the central nervous system.In the present study, the effects of electrophoretically administered S-6 on Renshaw cells were compared with the results seen with intravenous administration.The action of electrophoretically applied S-6 on the electrical activity of the Renshaw cells was also com pared with that of other cholinergic agents. MATERIALS AND METHODSExperiments were carried out on 29 adult cats anesthetized with pentobarbital sodium (35 mg/kg i.p.) and immobilized with gallamine triethiodide. The head and pelvis of the animal were stereotaxically fixed.Laminectomy was performed at levels from Ll to S2. The L7 ventral root was sectioned peripherally and the central end was placed on a bipolar platinum wire electrode for stimu lation by square pulses of 0.1 msec duration at a rate of 1 Hz.Double or triple barrel microelectrodes were used for electrophoretic application of S-6 and other drugs to Renshaw cells. Unitary activities of Renshaw cells were recorded extracellularly with one barrel filled with 4 M NaCI (tip resistance, 1-3 MQ). The other barrels were filled with one or two of the following drugs dissolved in 0.9% saline: S-6 (2 M, pH 3.9), methacholine bromide (Tokyo Kasei) (2 M, pH 3.2), acetylcholine chloride (Daiichi Seiyaku) (1 M, pH 4.1) and nicotine tartrate (Nakarai Kagaku Yakuhin) (1 M, pH 2.9). The tip resistances of drug-containing barrels were kept below 20 MQ to avoid