MECHANISM OF NICOTINE‐INDUCED RELEASE OF NORADRENALINE FROM ADRENERGIC NERVE ENDINGS

A study of the mechanism of release of [³H]‐noradrenaline ([³H]‐NA) by nicotine from isolated vas deferens of the rat was made using incubation media of different ionic composition. Nicotine (20 μg/ml)‐induced release of [³H]‐NA was significantly potentiated in K⁺‐free Krebs solution as compared to that in normal Krebs‐Ringer solution. Nicotine‐induced release of [³H]‐NA was significantly reduced in Na⁺‐deficient Krebs solution (containing only 11 mM Na⁺) and was abolished in Na⁺‐free Krebs solution. In totally depolarized tissues, nicotine failed to cause an outflow of [³H]‐NA but Ca²⁺ (5 mM) did so. Nicotine required the presence of Ca²⁺ in the incubation medium to cause release of [³H]‐NA from adrenergic nerve terminals, the magnitude of release being dependent upon the concentration of Ca²⁺. Nicotine‐induced release of [³H]‐NA was demonstrated in high Ca²+, Na⁺‐free Krebs solution in which all Na⁺ had been replaced with Ca²⁺. It is concluded that nicotine increases the membrane permeability to both Na⁺ and Ca²⁺. It is also suggested that the increase in permeability to Ca²⁺ alone is not sufficient but a local depolarizing action of nicotine is necessary to cause release of noradrenaline from adrenergic nerve endings. 1977 British Pharmacological Society