Mechanism of nicotine-evoked release of [3H]-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 [3H]-noradrenaline. NIC (10–1000 μM) increased [3H]-NA release in a concentration-dependent manner. NIC (100 μM)-evoked [3H]-NA release was largely dependent on external Ca2+, and was attenuated by ω-conotoxin GVIA (0.1 μM) but not by nitrendipine (1 μM). Tetrodotoxin (1 μM) and nisoxetine (0.1 μM) attenuated the NIC (100 μM)-evoked release of [3H]-NA. Mecamylamine (10 μM), dihydro-β-erythroidine (10 μM) and d-tubocurarine (30 μM), but not α-bungarotoxin (α-BTX, 0.1 μM), attenuated the NIC (100 μM)-evoked release of [3H]-NA. NIC (100 μM)-evoked release of [3H]-NA was not affected by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 30 μM) and D(−)-2-amino-5-phosphonopentanoic acid (D-AP5, 100 μM), but attenuated by MK-801 (10 μM). MK-801 (0.1–1000 μM) displaced the specific binding of [3H]-nisoxetine with Ki values of 91.2 μM. NIC (100, 300 and 1000 μM) did not induce [3H]-D-aspartate release in human cerebral cortex slices. NIC (100 μM)-evoked release of [3H]-NA was attenuated by 7-nitroindazole (10 μM), NG-nitro-L-arginine methyl ester HCl (L-NAME, 30 μM), NG-monomethyl-L-arginine acetate (L-NMMA, 300 μM). [3H]-NA release induced by NIC (100 μM) was attenuated by methylene blue (3 μM) and 1H-[1,2,4]oxadiazole[4,3-α]quinoxalin-1-one (ODQ, 10 μM), and enhanced by zaprinast (30 μM). In conclusion, NIC stimulates the release of [3H]-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