Mechanism of nicotine-induced release of noradrenaline from adrenergic nerve endings

Abstract

1 A study of the mechanism of release of [(3)H]-noradrenaline ([(3)H]-NA) by nicotine from isolated vas deferens of the rat was made using incubation media of different ionic composition.2 Nicotine (20 mug/ml)-induced release of [(3)H]-NA was significantly potentiated in K(+)-free Krebs solution as compared to that in normal Krebs-Ringer solution.3 Nicotine-induced release of [(3)H]-NA was significantly reduced in Na(+)-deficient Krebs solution (containing only 11 mM Na(+)) and was abolished in Na(+)-free Krebs solution.4 In totally depolarized tissues, nicotine failed to cause an outflow of [(3)H]-NA but Ca(2+) (5 mM) did so.5 Nicotine required the presence of Ca(2+) in the incubation medium to cause release of [(3)H]-NA from adrenergic nerve terminals, the magnitude of release being dependent upon the concentration of Ca(2+).6 Nicotine-induced release of [(3)H]-NA was demonstrated in high Ca(2+), Na(+)-free Krebs solution in which all Na(+) had been replaced with Ca(2+).7 It is concluded that nicotine increases the membrane permeability to both Na(+) and Ca(2+). It is also suggested that the increase in permeability to Ca(2+) alone is not sufficient but a local depolarizing action of nicotine is necessary to cause release of noradrenaline from adrenergic nerve endings.