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

• Published in: Brain research bulletin Vol. 62; no. 5; pp. 413 - 423
• Main Authors: Amtage, Florian, Neughebauer, Bogdan, McIntosh, J.Michael, Freiman, Thomas, Zentner, Josef, Feuerstein, Thomas J, Jackisch, Rolf
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2004
• Subjects: Acetylcholine - metabolism; Acetylcholine release; Adolescent; Adult; Animals; Autoreceptors; Electric Stimulation; Female; Glutamate release; Hippocampus - drug effects; Hippocampus - physiology; Humans; Male; Neocortex - drug effects; Neocortex - physiology; Nicotinic Antagonists - pharmacology; Norepinephrine - metabolism; Norepinephrine - pharmacology; Organ Culture Techniques; Presynaptic nicotine receptors; Rat hippocampus; Rat neocortex; Receptors, Glutamate - drug effects; Receptors, Glutamate - metabolism; Receptors, Nicotinic - drug effects; Receptors, Nicotinic - physiology; Species Specificity; α-Conotoxins; Glutamate release; Presynaptic nicotine receptors; Acetylcholine release; Rat neocortex; Rat hippocampus; α-Conotoxins
• ISSN: 0361-9230; 1873-2747
• DOI: 10.1016/j.brainresbull.2003.11.002

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.