Characterization of nicotinic receptors inducing noradrenaline release and absence of nicotinic autoreceptors in human neocortex

Presynaptic facilitatory nicotinic receptors (nAChRs) on noradrenergic axon terminals were studied in slices of human or rat neocortex and of rat hippocampus preincubated with [ 3 H ]noradrenaline ([ 3 H ]NA). During superfusion of the slices, stimulation by nicotinic agonists for 2 min only slightly increased [ 3 H ]NA outflow in the rat neocortex, but caused a tetrodotoxin-sensitive, Ca 2+-dependent release of [ 3 H ]NA in rat hippocampus and human neocortex. In both tissues a similar rank order of potency of nicotinic agonists was found: epibatidine⪢DMPP>nicotine∼cytisine≥acetylcholine; choline was ineffective. In human neocortex, the effects of nicotine (100 μM) were reduced by mecamylamine, methyllycaconitine, di-hydro-β-erythroidine (10 μM, each) and the α 3β 2/α 6β x -selective α-conotoxin MII (100/200 nM). The α 3β 4 selective α-conotoxin AuIB (1 μM), and the α 7 selective α-conotoxin ImI (200 nM) as well as α-bungarotoxin (125 nM) were ineffective. Glutamate receptor antagonists (300 μM AP-5, 100 μM DNQX) acted inhibitory, suggesting the participation of nAChRs on glutamatergic neurons. On the other hand, nAChR agonists were unable to evoke exocytotic release of [ 3 H ]acetylcholine from human and rat neocortical slices preincubated with [ 3 H ]choline. In conclusion: (1) α 3β 2 and/or α 6 containing nAChRs are at least partially responsible for presynaptic cholinergic facilitation of noradrenergic transmission in human neocortex; (2) nicotinic autoreceptors were not detectable in rat and human neocortex.