Mechanism of nicotine‐evoked release of [ 3 H]‐noradrenaline in human cerebral cortex slices

The mechanism of stimulation of noradrenaline (NA) release by nicotine (NIC) was investigated in human cerebral cortex slices preloaded with [ 3 H]‐noradrenaline. NIC (10–1000 μ M ) increased [ 3 H]‐NA release in a concentration‐dependent manner. NIC (100 μ M )‐evoked [ 3 H]‐NA release was largely dependent on external Ca 2+ , and was attenuated by ω‐conotoxin GVIA (0.1 μ M ) but not by nitrendipine (1 μ M ). Tetrodotoxin (1 μ M ) and nisoxetine (0.1 μ M ) attenuated the NIC (100 μ M )‐evoked release of [ 3 H]‐NA. Mecamylamine (10 μ M ), dihydro‐β‐erythroidine (10 μ M ) and d ‐tubocurarine (30 μ M ), but not α‐bungarotoxin (α‐BTX, 0.1 μ M ), attenuated the NIC (100 μ M )‐evoked release of [ 3 H]‐NA. NIC (100 μ M )‐evoked release of [ 3 H]‐NA was not affected by 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione (CNQX, 30 μ M ) and D(−)‐2‐amino‐5‐phosphonopentanoic acid (D‐AP5, 100 μ M ), but attenuated by MK‐801 (10 μ M ). MK‐801 (0.1–1000 μ M ) displaced the specific binding of [ 3 H]‐nisoxetine with K i values of 91.2 μ M . NIC (100, 300 and 1000 μ M ) did not induce [ 3 H]‐D‐aspartate release in human cerebral cortex slices. NIC (100 μ M )‐evoked release of [ 3 H]‐NA was attenuated by 7‐nitroindazole (10 μ M ), N G ‐nitro‐ L ‐arginine methyl ester HCl ( L ‐NAME, 30 μ M ), N G ‐monomethyl‐ L ‐arginine acetate ( L ‐NMMA, 300 μ M ). [ 3 H]‐NA release induced by NIC (100 μ M ) was attenuated by methylene blue (3 μ M ) and 1 H ‐[1,2,4]oxadiazole[4,3‐α]quinoxalin‐1‐one (ODQ, 10 μ M ), and enhanced by zaprinast (30 μ M ). In conclusion, NIC stimulates the release of [ 3 H]‐NA through activation of α‐BTX‐insensitive nicotinic acetylcholine receptors in the human cerebral cortex slices and this action of NIC is associated with modulation of the NO/cGMP pathway.British Journal of Pharmacology (2002) 137 , 1063–1070. doi: 10.1038/sj.bjp.0704975