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Neurotransmitters

Neurotransmitters. Lesson 13. Neurotransmitters. Chemical messengers Signal between cells Released at axon terminal By action potentials Metabolism by enzymes Synthesis (anabolism) Degradation (catabolism) ~. Chemical Signaling. Otto Loewi had a dream Chemical Signal?

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Neurotransmitters

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  1. Neurotransmitters Lesson 13

  2. Neurotransmitters • Chemical messengers • Signal between cells • Released at axon terminal • By action potentials • Metabolism by enzymes • Synthesis (anabolism) • Degradation (catabolism) ~

  3. Chemical Signaling • Otto Loewi had a dream • Chemical Signal? • How can it be demonstrated? • Frog Heart Preparation ~

  4. electrical stimulation - • Stimulate Vagus • Heart rate slows ~

  5. - • Stimulate A • Collect fluid ~ B A

  6. - • Perfuse heart B • Heart B slows • chemical = vagusstoff ~ B A

  7. Repeat w/ accelerator nerve • HR increases • Acceleransstoff ~ + B A

  8. The Chase Is On • Search for chemical neurotransmitters (NT) • Criteria • Found in axon terminals • Released by action potentials • Synthesis identified • External application mimic normal response • Externally applied same mechanism as NT ~

  9. Acetylcholine - ACh • Loewi’s vagusstoff • Peripheral N.S. • Skeletal muscle contraction • Autonomic NS • Ganglia • Parasympathetic neuroeffector junction • Central N.S. - widespread • Hippocampus • Hypothalamus ~

  10. Acetylcholine - ACh • Receptor subtypes • Nicotinic (nACh-R) • ionotropic • Muscarinic (mACh-R) • metabotropic • Degraded by acetylcholinesterase • AChE • Enzyme found in synapse ~

  11. choline acetyltransferase ACh ACh Synthesis choline + acetyl CoA

  12. Monoamines • 2 groups • Amino acid precursors • Catecholamines - tyrosine • Indolamine - tryptophan • All degrade by monoamine oxidase (MAO) • Affected by many of same enzymes & drugs ~

  13. Catecholamines Dopamine - DA Dopaminergic Norepinephrine - NE Noradrenergic Epinephrine - E Adrenergic ~ Indolamines Serotonin - 5HT Serotonergic Monoamines

  14. Dopamine • Only in central nervous system • mostly inhibitory systems • Reward • Schizophrenia • Movement • Nigrostriatal Pathway • At least 5 DA-R types: D1, D2, etc. ~

  15. Norepinephrine • Loewi’s acceleranstoff • Peripheral N.S. • Sympathetic neuroeffector junction • Adrenal glands • Central N.S. • Hypothalamus • Locus coeruleus • Alpha & Beta receptor subtypes • NEa & NEb ~

  16. Serotonin • NOT a catecholamine • Peripheral • 98% in blood & smooth muscle • Central N.S. • Raphe nucleus • Hypothalamus • R subtypes: 5HT1 & 5HT2 ~

  17. Amino Acid Neurotransmitters • Unmodified amino acids • Nonessential amino acids • Glutamate • Primary NT in CNS excitatory neurons • Metabotropic (mGlu-R) • Iononotropic: NMDA-R; AMPA-R • Excitotoxicity • Following brain injury • Elevated Glu activity

  18. Amino Acid Neurotransmitters • GABA – GABAergic • g-aminobutyric acid • Major NT in brain inhibitory system • Receptor subtypes • GABAA - controls Cl- channel • GABAB - controls K+ channel ~

  19. Neuropeptides • Chains of amino acids • Synthesis in soma • Axonal transport • Often neuromodulators • alters sensitivity of neurons • slower, longer-lasting effects • Substance P - pain signaling ~

  20. Neuropeptides: Endorphins • Endogenous + morphine = Endorphin • Also opioids • Opiate drugs are ligands • analgesia, euphoria ~

  21. Some Other NTs • Histamine • Inflammatory Response • Nitric Oxide - It’s a gas • Retrograde messenger • Not stored in vesicles • Endocannabinoids • Anandamide, 2 - AG • Purines • ATP, GTP ~

  22. Focus on • ACh • NE • DA • 5HT • GABA • Endorphins

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