Acetylcholine (ACH) Acetyl-CoA + Cholin ACH +CoA Choline-acetyl-transferase (CAT) Acetyl-CoA +...
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Transcript of Acetylcholine (ACH) Acetyl-CoA + Cholin ACH +CoA Choline-acetyl-transferase (CAT) Acetyl-CoA +...
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Acetylcholine (ACH)
Acetyl-CoA + Cholin ACH +CoA
Choline-acetyl-transferase (CAT)
Acetyl-CoA + Cholin ACH +CoA
Acetylcholine-esterase
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TrimethylAmino-Ethanol
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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
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Postsynaptic ACH receptors
Nicotinic receptorIonotropic, cation (Na+) channel
Pentameric: 5 transmembrane proteins=subunits 2 α, 1β, 1γ, 1δ
in the brain: hetero-pentameric: α2-8, β2-4 homo-pentameric: α7, 8
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Muscarinic receptors M1 – M5
metabotropicexcitatory: 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-receptorsN receptor: positive feed-back, fast onset fast desensitizationM receptor negative feed back, slow onset slow desensitization
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Acetylcholine AgonistsDirect Parasympathomimetics
Rezeptor Agonist
N Nicotine
M MuskarinPilocarpin
M, N CarbacholArecolin
Indirect ACH-AgonistsIndirect Parasympathomimetics
mode of action:ACH-Esterase inhibition
reversible inhibitors:PhysostigmineEserineNeostigmine
irreversible inhibitors:ParathioneNitrostigmineE 605Sarin, Tabun, Soman
ACH-AntagonistsDirect Parasympatholytics
M Belladonna AlkaloidsScopolamineAtropinePirenzepine
N CurareGallamin, FlaxedilSuxamethoniumMecamylamine, Hexamethonium
Indirect ACH-AntagonistsIndirect Parasympatholytics
HemicholinumBotulinus Toxin
Neuropharmacology Uni-Tuebingen
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Cotransmitters of ACH
Cortex of the rat: Vasoactive intestinal peptide (VIP)N. Cochlearis: EncephalinNBM/ Septum: Substance PATP
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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)
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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)
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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.
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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