Mechanism of nicotine-induced release of norepinephrine from adrenergic nerve endings: is generation and propagation of impulses necessary?

The mechanism of release of 3H-norepinephrine (3H-NE) from adrenergic nerve endings by nicotine was investigated. Tetrodotoxin (5 X 10(-7) g/ml) abolished the contractile response of adrenergically innervated tissues, namely, rat isolated vas deferens, cat splenic strips, guinea-pig atria to transmural stimulation but not to nicotinic agents, and it did not affect the release of 3H-NE by nicotine from rat isolated vas deferens. Incubation of tissues in low Na+ (23 mM) and high K+ (50 mM) medium, which is known to inhibit propagation of nerve impulses, did not affect the nicotine-induced outflow of 3H-NE. These observations support the contention that the generation of action potential in the postganglionic sympathetic nerve fibres is not the cause of release of norepinephrine by nicotinic agents.