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Acetylcholine (ACH) Acetyl-CoA + Cholin ACH +CoA

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1 Acetylcholine (ACH) Acetyl-CoA + Cholin ACH +CoA
Choline-acetyl-transferase (CAT) Acetylcholine-esterase

2 Trimethyl Amino- Ethanol

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


5 Postsynaptic ACH receptors
Nicotinic receptor Ionotropic, 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


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

8 Neuropharmacology Uni-Tuebingen
Acetylcholine Agonists Direct Parasympathomimetics Rezeptor Agonist N Nicotine M Muskarin Pilocarpin M, N Carbachol 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 M Belladonna Alkaloids Scopolamine Atropine Pirenzepine N Curare Gallamin, Flaxedil Suxamethonium Mecamylamine, Hexamethonium Indirect ACH-Antagonists Indirect Parasympatholytics Hemicholinum Botulinus Toxin Neuropharmacology Uni-Tuebingen

9 Cotransmitters of ACH Cortex of the rat: Vasoactive intestinal peptide (VIP) N. Cochlearis: Encephalin NBM/ Septum: Substance P ATP


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)

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: –10 % are ACH ergic Nucleus basalis whole cortex Septum hippocampus PPTg VTA (mesencephalon)

13 Figure: Central cholinergic pathways
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.

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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