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Neuropharmacology: Neurotransmission
 

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, ...

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 Neuropharmacology: Neurotransmission Presentation Transcript

    • Neurocommunication Brian J. Piper, Ph.D.
    • 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
    • Goals• Neurotransmission – History – Onset: Neurotransmitter release (classical and non-classical) – Offset: autoreceptors, transporters, enzymes – Receptor Families• Endocrine
    • History: Golgi vs. Cajal• Italian physician• Reticulum theory• Silver stain Camillo Golgi (1843-1926)
    • Controversy: Golgi vs. Cajal • Santiogo Ramon y Cajal – Neuroanatomist – Used Golgi’s technique – Neuron theory1852-1934 Chicken cerebellum
    • Neural Communication The body’s information system is built frombillions of interconnected cells called neurons. Communication between neurons is both electrical and chemical.
    • Otto Loewi• Discovered “Vagusstoff” later known as acetylcholine• “father of neuroscience”• Nobel Prize 1936
    • What are amino acids?• Amine (NH2) + Carboxyl ( -COOH)• 20 total, 9 essential tyrosine Tryptophan
    • 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
    • More terminology• Peptides: short (<50) strings of amino acids, Valine-Glycine-Serine-Alanine… e.g. NPY
    • More terminologyProteins: longer strings of amino acids, have 3-Dstructure, form receptors, transporters
    • Comparison Peptide ProteinSize (amino acids) < 40 >40Dimensions 1-D 3-DComplexity Low High Hemoglobin
    • “Typical” Synapse
    • Electron Microscope• Beams of electrons are presented to a thin section, 50 pm (10-12) resolution• Reveals different types of Synapses
    • Dendritic Spine
    • Axodendritic Synapse
    • Axosomatic Synapse
    • 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”
    • Neurotransmitter Comparison Classical Non-ClassicalDiscovery 1950’s 1980’sConcentration High Low# Few ManySynthesis Anywhere Soma
    • Classical Neurotransmitters• Monoamines: dopamine, norepinephrine, serotonin• Acetylcholine (ACh)• Amino Acids: glycine, GABA, Glutamate
    • Non-classical Neurotransmitters• Peptides: Corticotropin-releasing factor (CRF), endorphins• Lipids: Anandamide• Gases: Nitric Oxide
    • 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.
    • Axon Terminal
    • 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
    • Brakes I• Enzyme: A + B __ENZ____> AB• Enzyme: CD __ENZ____> C + D
    • Transporters• Proteins that move molecule from one place to another, examples: – SERT: serotonin transporter – NET: norepinephrine transporter – DAT: dopamine transporter Inside ---------------------------------------------------------------------- Outside
    • 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)
    • Types of Receptors
    • So Many Receptors! Serotonin (5-HT): 1 2 3 4 5 6 7
    • Family 1: Ionotropic• Binding to receptor opens channel to let ions in (aka: ligand gated ion receptors)
    • 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
    • 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
    • Family 2: Metabotropic (Channel)• Steps:• 1) Ligand binds receptor• 2) G protein alters channel• 3) ions flow out of neuron
    • 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
    • Family 3: Tyrosine Kinase• Steps:1) Ligand (BDNF) binds to Trk receptor2) Trk receptors come together, andphosphorylate each other
    • So many drug targets!!! Examples: 1) Tryptophan 6) Nicotine 10) MAO-I 11) SSRIs
    • 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)
    • 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.
    • Reference