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Acetylcholine & Other Neurotransmitters

Acetylcholine & Other Neurotransmitters. Lesson 10. Acetylcholine - ACh. Peripheral N.S. Skeletal muscle contraction Autonomic NS Ganglia Parasympathetic neuroeffector junction Central N.S. - widespread Hippocampus Hypothalamus ~. Acetylcholine - ACh .

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Acetylcholine & Other Neurotransmitters

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  1. Acetylcholine & Other Neurotransmitters Lesson 10

  2. Acetylcholine - ACh • Peripheral N.S. • Skeletal muscle contraction • Autonomic NS • Ganglia • Parasympathetic neuroeffector junction • Central N.S. - widespread • Hippocampus • Hypothalamus ~

  3. Acetylcholine - ACh • Receptor subtypes: 2 major groups • Nicotinic receptors - ionotropic • excitatory • Muscarinic receptors - metabotropic • excitatory or inhibitory • Degraded by acetylcholinesterase- • AChE • Membrane bound - • pre- & postsynaptic membrane -~

  4. choline acetyltransferase ACh ACh Synthesis choline + acetyl CoA

  5. Cholinergic Agonists • Direct • Muscarine • Nicotine • small doses ~

  6. AChE inhibitors • Physostigmine • Organophosphates - irreversible • DFP • Soman & Sarin • Malathion • Agonist or Antagonist? indirect agonist ~

  7. Cholinergic Antagonists • Direct • Nicotinic - Curare • Muscarinic - Atropine Scopolamine • Indirect • Hemicholinium • Botulinus Toxin • Black Widow Spider Venom ~

  8. Botulinus toxin BWSV AChE AChE ACh N M curare atropine

  9. Excitatory Amino Acids: Glutamate • Primary NT in CNS excitatory neurons • Nonessential amino acids • Synthesis • Precursor glutamine from astroglia • Termination • presynaptic & glial reuptake ~

  10. Excitatory Amino Acids: Glutamate • Receptor subtypes • Metabotropic (mGlu-R) • Inhibition of Na+ & Ca++ channels • Iononotropic: NMDA-R; AMPA-R • nonselective • Excitotoxicity • Following brain injury • Elevated Glu activity • Aspartate ~

  11. Inhibitory Amino Acids: Glycine • Primarily spinal cord • Cl- channels • Strychnine is antagonist ~

  12. Inhibitory Amino Acids: GABA • GABA - GABAergic • Major NT in brain inhibitory system • Receptor subtypes • GABAA - controls Cl- channel • GABAB - controls K+ channel • Degradation by GABA-T • GABA aminotransferase ~

  13. glutamate decarboxylase glutaminase Glutamate GABA GABA Synthesis Glutamine

  14. GABAergic Drugs • Agonists • Benzodiazepines • Barbiturates • Ethyl alcohol (ETOH) • Antagonists • Picrotoxin • Inverse agonist • Ro 15-4513 • ßCCM ~

  15. Neuropeptides • Chains of amino acids • Synthesis in soma • Often neuromodulators • Substance P - pain • Endorphins - analgesia, euphoria ~

  16. Endorphins • Opioids • Dynorphin • met-enkephalin • leu-enkephalin • Beta-endorphin • Receptor subtypes: • m1, m2, k, d ~

  17. Endorphins • Agonists • morphine • heroin • codeine • Antagonists • naloxone • naltrexone ~

  18. Some Other NTs • Histamine • Inflammatory Response • Nitric Oxide - It’s a gas • Retrograde messenger • Ca++-dependent • Not stored in vesicles ~

  19. Some Other NTs • Endocannabinoids • Anandamide • 2 - AG • Inhibits presynaptic GABA release • Synthesis by enzymatic degradation of membrane ~

  20. Focus on ACh NE DA 5HT GABA Endorphins

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