The effect of nicotine and cytisine on3H-acetylcholine release from cortical slices of guinea-pig brain

Summary Nicotine 1.8×10^–5–1.8×10^–4 mol/l enhanced the spontaneous³H-efflux from guinea-pig cortical slices preloaded with³H-choline and perfused in the presence of hemicholinium (HC-3).The facilitation of tritium outflow was prevented by tetrodotoxin 5×10^–7 mol/l and byd-tubocurarine 4.5×10^–6 mol/l. Nicotine 1.8×10^–6–1.8×10^–4 mol/l, and the agonist cytisine 5×10^–7–5×10^–5 mol/l increased, in a concentration-dependent way,³H-efflux from electrically-stimulated slices (0.2 Hz). The concentration-response curves of both drugs were parallelly shifted to the right byd-tubocurarine 4.5×10^–6 mol/l. The EC₅₀ values (i.e. the concentrations required to cause a 50% increase in the S₂/S₁ ratio) changed for nicotine from 5.58×10^–5 to 4.34×10^–4 and for cytisine from 6.3×10^–6 to 2.75×10^–4 mol/l in the absence and in the presence of the antagonist, respectively.In the range of 0.2–2 Hz the magnitude of the effect of nicotine was inversely related to the rate of stimulation.The response to nicotine was subject to rapidly developing tachyphylaxis; it was resistant to atropine.It is concluded that nicotine and cytisine facilitate³H-efflux from the cholinergic nerve endings of guinea-pig cerebral cortex. This effect involves sodium-dependent mechanisms and is due to an interaction of the drugs with receptors showing affinity ford-tubocurarine.