No abstract

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.

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A method for the extraction, separation and quantitative determination of [3H]noradrenaline [3H-NA] and its five major metabolites has been devised using thin layer chromatography. This procedure was used to study the pattern of 3H-NA and its metabolites in the total radioactivity of the tissues and that released spontaneously from the rat isolated vas deferens. Whereas in tissues 3H-NA represented almost all of the total radioactivity (94-8+/-0.47%), in the samples of spontaneous outflow it represented only 16-8+/-2.1%. The rest was mostly accounted for by the five metabolites, primarily 3H-DOPEG and 3H-MOPEG. These findings show that in the rat vas deferens 3H-NA is preferentially metabolized via the two glycol derivatives, i.e. 3H-DOPEG and 3H-MOPEG.

The calcium-magnesium (Ca2+-Mg2+) interaction in the process of nicotine-induced release of [3H]noradrenaline ([3H]NA) from rat isolated vas deferens was studied. Increasing extracellular concentrations of Mg2+ caused a dose-dependent depression of release of [3H]NA by nicotine, and this inhibitory effect of Mg2+ was overcome by raising the concentration of CA2+. It is concluded that Mg2+ antagonizes the nicotine-induced increase in the Ca2+ influx into the adrenergic nerve terminals, and that nicotine acts on adrenergic neuronal membrane rather than intraneuronally to cause release of NA.