Nicotine-induced release of noradrenaline and neuropeptide Y in guinea pig heart.

The effect of nicotine on the release of noradrenaline and neuropeptide Y was investigated in isolated perfused guinea pig hearts (Langendorff technique). Endogenous noradrenaline, dihydroxyphenylglycol (both determined by high pressure liquid chromatography) and neuropeptide Y (determined by radioimmunoassay) were measured in the coronary venous effluent following the addition of nicotine to the perfusate. Nicotine (2 microM to 2 mM) dose-dependently increased both noradrenaline and neuropeptide Y overflow, and the release of both transmitters was closely correlated (r = 0.81). Despite ongoing nicotine administration noradrenaline and neuropeptide Y levels returned to basal values within 6 min of continuous nicotine administration indicating rapid tachyphylaxis to the effect of nicotine. The nicotine-induced release of noradrenaline and neuropeptide Y required the presence of extracellular calcium, and the release of both substances was suppressed by hexamethonium or by low concentrations of the inhibitors of the neuronal noradrenaline uptake (uptake1) desipramine and nisoxetine. Nicotine did not result in a significant release of the noradrenaline metabolite dihydroxyphenylglycol which was utilized as an indicator of free axoplasmic amine levels. The close correlation between noradrenaline and neuropeptide Y release, its calcium dependence, and the lack of dihydroxyphenylglycol overflow are in agreement with the concept of a common and exocytotic release of noradrenaline and neuropeptide Y induced by nicotine.