title: Characterization of nicotinic receptors inducing noradrenaline release and absence of nicotinic autoreceptors in human neocortex.
abstract: 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.
authors.affiliation: Neuropharmakologisches Labor Institut für Experimentelle und Klinische Pharmakologie und Toxikologie der Universität Freiburg, Hansastr 9A, D-79104 Freiburg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Amtage
authors.forename: Bogdan
authors.initials: B
authors.lastname: Neughebauer
authors.forename: J Michael
authors.initials: JM
authors.lastname: McIntosh
authors.forename: Thomas
authors.initials: T
authors.lastname: Freiman
authors.forename: Josef
authors.initials: J
authors.lastname: Zentner
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Feuerstein
authors.forename: Rolf
authors.initials: R
authors.lastname: Jackisch
mesh_terms: 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
chemical_list: D017660:Autoreceptors; D018733:Nicotinic Antagonists; D017470:Receptors, Glutamate; D011978:Receptors, Nicotinic; D000109:Acetylcholine; D009638:Norepinephrine