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 [3H]noradrenaline ([3H]NA). During superfusion of the slices, stimulation by nicotinic agonists for 2 min only slightly increased [3H]NA outflow in the rat neocortex, but caused a tetrodotoxin-sensitive. Ca(2+)-dependent release of [3H]NA in rat hippocampus and human neocortex. In both tissues a similar rank order of potency of nicotinic agonists was found: epibatidine >> DMPP > nicotine approximately cytisine > or = acetylcholine; choline was ineffective. In human neocortex, the effects of nicotine (100 microM) were reduced by mecamylamine, methyllycaconitine, di-hydro-beta-erythroidine (10 microM, each) and the alpha3beta2/alpha6betax-selective alpha-conotoxin MII (100/200 nM). The alpha3beta4 selective alpha-conotoxin AuIB (1 microM), and the alpha7 selective alpha-conotoxin ImI (200 nM) as well as alpha-bungarotoxin (125 nM) were ineffective. Glutamate receptor antagonists (300 microM AP-5, 100 microM DNQX) acted inhibitory, suggesting the participation of nAChRs on glutamatergic neurons. On the other hand, nAChR agonists were unable to evoke exocytotic release of [3H]acetylcholine from human and rat neocortical slices preincubated with [3H]choline.


CONCLUSIONS
(1) alpha3beta2 and/or alpha6 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.
Amtage
Florian
F
Neuropharmakologisches Labor Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Universität Freiburg, Hansastr 9A, D-79104 Freiburg, Germany.
Neughebauer
Bogdan
B
McIntosh
J Michael
JM
Freiman
Thomas
T
Zentner
Josef
J
Feuerstein
Thomas J
TJ
Jackisch
Rolf
R
D000109:Acetylcholine / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000818:Animals; D017660:Autoreceptors; D004558:Electric Stimulation; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D008297:Male; D019579:Neocortex / Q000187:drug effects / Q000502:physiology*; D018733:Nicotinic Antagonists / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D009924:Organ Culture Techniques; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D013045:Species Specificity
D017660:Autoreceptors; D018733:Nicotinic Antagonists; D017470:Receptors, Glutamate; D011978:Receptors, Nicotinic; D000109:Acetylcholine; D009638:Norepinephrine