Neuropharmacology: Neurotransmission

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Lecture 6 from a college level neuropharmacology course taught in the spring 2012 semester by Brian J. Piper, Ph.D. (psy391@gmail.com) at Willamette University. Includes neurotransmitter release, reuptake, and inactivation

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Neuropharmacology: Neurotransmission

  1. 1. Neurocommunication Brian J. Piper, Ph.D.
  2. 2. Terminology• Neurotransmitter: chemical that is released in the brain and has an effect on a local target• Hormone: chemical that is released into bloodstream that has an effect on a distant target
  3. 3. Goals• Neurotransmission – History – Onset: Neurotransmitter release (classical and non-classical) – Offset: autoreceptors, transporters, enzymes – Receptor Families• Endocrine
  4. 4. History: Golgi vs. Cajal• Italian physician• Reticulum theory• Silver stain Camillo Golgi (1843-1926)
  5. 5. Controversy: Golgi vs. Cajal • Santiogo Ramon y Cajal – Neuroanatomist – Used Golgi’s technique – Neuron theory1852-1934 Chicken cerebellum
  6. 6. Neural Communication The body’s information system is built frombillions of interconnected cells called neurons. Communication between neurons is both electrical and chemical.
  7. 7. Otto Loewi• Discovered “Vagusstoff” later known as acetylcholine• “father of neuroscience”• Nobel Prize 1936
  8. 8. What are amino acids?• Amine (NH2) + Carboxyl ( -COOH)• 20 total, 9 essential tyrosine Tryptophan
  9. 9. More terminology• Peptides: short (<50) strings of amino acids, Valine-Glycine-Serine-Alanine… e.g. NPY C terminal: COOH N terminal: NH2 Arginine, Proline, Lysine, Phenylalanine, Methionine, Histidine, Aspartic Acid, Valine
  10. 10. More terminology• Peptides: short (<50) strings of amino acids, Valine-Glycine-Serine-Alanine… e.g. NPY
  11. 11. More terminologyProteins: longer strings of amino acids, have 3-Dstructure, form receptors, transporters
  12. 12. Comparison Peptide ProteinSize (amino acids) < 40 >40Dimensions 1-D 3-DComplexity Low High Hemoglobin
  13. 13. “Typical” Synapse
  14. 14. Electron Microscope• Beams of electrons are presented to a thin section, 50 pm (10-12) resolution• Reveals different types of Synapses
  15. 15. Dendritic Spine
  16. 16. Axodendritic Synapse
  17. 17. Axosomatic Synapse
  18. 18. Neurotransmitter Criteria• 1) Found and made presynaptically.• 2) Mechanism for inactivation.• 3) Stimulating neuron releases it.• 4) Receptors found postsynaptically.• 5) Applying substance has biological effect.• 6) Antagonizing inhibits biological effect. “neuromodulators”
  19. 19. Neurotransmitter Comparison Classical Non-ClassicalDiscovery 1950’s 1980’sConcentration High Low# Few ManySynthesis Anywhere Soma
  20. 20. Classical Neurotransmitters• Monoamines: dopamine, norepinephrine, serotonin• Acetylcholine (ACh)• Amino Acids: glycine, GABA, Glutamate
  21. 21. Non-classical Neurotransmitters• Peptides: Corticotropin-releasing factor (CRF), endorphins• Lipids: Anandamide• Gases: Nitric Oxide
  22. 22. Co-Transmitters Amine/Amino Acid Peptide Dopamine Cholecystokinin (CCK) Norepinephrine enkephalin Epinephrine neurotensin Serotonin substance P Acetylcholine somatostatin Gamma aminobutyric acid (GABA) motilinStahl, S. (2000). Essential Psychopharmacology, p. 20.
  23. 23. Axon Terminal
  24. 24. Brakes II• Autoreceptors: this receptor (“auto” = “self”) can act to inhibit further neurotransmitter release – Terminal (axon) autoreceptors: inhibit neurotransmitter release – Somatodendritic autoreceptors: reduce rate of action potentials
  25. 25. Brakes I• Enzyme: A + B __ENZ____> AB• Enzyme: CD __ENZ____> C + D
  26. 26. Transporters• Proteins that move molecule from one place to another, examples: – SERT: serotonin transporter – NET: norepinephrine transporter – DAT: dopamine transporter Inside ---------------------------------------------------------------------- Outside
  27. 27. Post-synaptic• Ligand: substance that binds to a receptor• Ion: atom where # electrons ≠ # protons – Ca2+ Na+ K+ – Cl-• First messenger: neurotransmitter• Second messenger: other molecule• Kinase: enzyme that adds phosphate (PO4)
  28. 28. Types of Receptors
  29. 29. So Many Receptors! Serotonin (5-HT): 1 2 3 4 5 6 7
  30. 30. Family 1: Ionotropic• Binding to receptor opens channel to let ions in (aka: ligand gated ion receptors)
  31. 31. Family 1: Ionotropic • Binding to receptor opens channel to let ions in (aka: ligand gated ion receptors)0:40 – 6:20: http://www.youtube.com/watch?v=8jPH2pKzIDY
  32. 32. Family 2: Metabotropic (2nd messenger)• Steps:• 1) Ligand binds receptor• 2) G protein acts on enzyme• 3) Enzyme regulates 2nd messenger• 4) 2nd messenger acts on protein kinase 6:30-9:00 http://www.youtube.com/watch?v=8jPH2pKzIDY
  33. 33. Family 2: Metabotropic (Channel)• Steps:• 1) Ligand binds receptor• 2) G protein alters channel• 3) ions flow out of neuron
  34. 34. Receptor Families Compared Ionotropic MetabotropicSubunits 4-5 1Mechanism Simple: Channel opening Complex: G protein cascade2nd messengers No YesSpeed Fast Slow Meyer & Quenzer (2005). p 73
  35. 35. Family 3: Tyrosine Kinase• Steps:1) Ligand (BDNF) binds to Trk receptor2) Trk receptors come together, andphosphorylate each other
  36. 36. So many drug targets!!! Examples: 1) Tryptophan 6) Nicotine 10) MAO-I 11) SSRIs
  37. 37. Endocrine SystemGland Hormone (Function)Pineal Melatonin (light-dark rhythm)Thyroid T3/T4 (energy)Adrenal Cortisol (stress)Pancreas Insulin (glucose)Ovaries Estrogens (2nd sex characteristics)Testes Androgens (2nd sex characteristics)
  38. 38. Example • Rats that received ecstasy (MDMA) during adolescence were more sensitive to a 5-HT2 agonist when adultsBiezonski et al. (2009). Brain Research, 1252, 87-93.
  39. 39. Reference

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