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holine (ACH) oA + Cholin A Choline-acetyl-transferase (C oA + Cholin A Acetylcholine-esterase
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Acetylcholine (ACH) Acetyl-CoA + Cholin ACH +CoA Choline-acetyl-transferase (CAT) Acetyl-CoA + Cholin ACH +CoA Acetylcholine-esterase.

Mar 26, 2015

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Acetylcholine (ACH) Acetyl-CoA + Cholin ACH +CoA Choline-acetyl-transferase (CAT) Acetyl-CoA + Cholin ACH +CoA Acetylcholine-esterase Slide 2 Trimethyl Amino- Ethanol Slide 3 ACH synapse Presynpase acetate + choline ACH transporter----------------------------------------------choline------------ Synaptic cleft ACH-esterase --------------------------------------------------------------------------------- Postsynapse excitatory R: Ionotropic: Nicotin R metab.: Muscarinic R inhibitory R: metab.: Muscarinic R Slide 4 Slide 5 Postsynaptic ACH receptors Nicotinic receptor Ionotropic, cation (Na+) channel Pentameric: 5 transmembrane proteins=subunits 2 , 1, 1, 1 in the brain: hetero-pentameric: 2-8, 2-4 homo-pentameric: 7, 8 Slide 6 Slide 7 Muscarinic receptors M1 M5 metabotropic excitatory: slow long lasting depolarisation due to closure of the K+ channel M1, M3, M5 inhibitory: slow long lasting hyperpolarisation due to opening of the K+ channel M2, M4 ACH auto-receptors N receptor: positive feed-back, fast onset fast desensitization M receptor negative feed back, slow onset slow desensitization Slide 8 Acetylcholine Agonists Direct Parasympathomimetics RezeptorAgonist NNicotine MMuskarin Pilocarpin M, NCarbachol Arecolin Indirect ACH-Agonists Indirect Parasympathomimetics mode of action: ACH-Esterase inhibition reversible inhibitors: Physostigmine Eserine Neostigmine irreversible inhibitors: Parathione Nitrostigmine E 605 Sarin, Tabun, Soman ACH-Antagonists Direct Parasympatholytics MBelladonna Alkaloids Scopolamine Atropine Pirenzepine NCurare Gallamin, Flaxedil Suxamethonium Mecamylamine, Hexamethonium Indirect ACH-Antagonists Indirect Parasympatholytics Hemicholinum Botulinus Toxin N europharmacology Uni-Tuebingen Slide 9 Cotransmitters of ACH Cortex of the rat: Vasoactive intestinal peptide (VIP) N. Cochlearis: Encephalin NBM/ Septum: Substance P ATP Slide 10 Slide 11 Specific toxins for ACH neurons AF 64: CAT inactivation inhibits the transporter (by alcylation) 192 IgG-Saporin: Immunotoxin antibody against p75NGF (=low affinity NGF receptor which is localized upon ACH neurons) Slide 12 Anatomy of the ACH System Periphery: Motor end plate Vegetaive NS: Sympathicus preganglionic: ACH - N receptor postganglionic: Noradrenalin Parasympath. preganglionic: ACH N receptor postanglionic: ACH M receptor Brain: 5 10 % are ACH ergic Nucleus basalis whole cortex Septum hippocampus PPTg VTA (mesencephalon) Slide 13 Figure: Central cholinergic pathways. The six major cholinergic projection groups (sectors) are depicted (Ch1-Ch6). Therein, projections from Ch1/Ch2 and Ch4 to hippocampal, limbic and neocortical areas are implicated in learning and memory processes. Slide 14 Physiology/Pathophysiology of ACH Septum hippocampus: learning, M-receptor mediated hippocampal theta rhythm transiently during orienting behaviour M-receptor mediated NBM - cortex learning N+M receptor mediated attention PPTg VTA brain reward

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