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~BN13 neurotransmitters.ppt

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~BN13 neurotransmitters.ppt

  1. 1. Neurotransmitters Lecture 13
  2. 2. CRITERIA <ul><li>NT found in axon terminals </li></ul><ul><li>NT released by action potentials </li></ul><ul><li>Synthesis identified </li></ul><ul><li>External application mimic normal Response </li></ul><ul><li>Pharmacology same for normal and externally applied NT ~ </li></ul>
  3. 3. Lock & Key Model <ul><li>NT binds to receptor </li></ul><ul><li>NT = key </li></ul><ul><li>Receptor = lock </li></ul><ul><li>Receptor changes shape </li></ul><ul><li>determines if EPSP or IPSP </li></ul><ul><li>receptor subtypes </li></ul><ul><li>NOT NT ~ </li></ul>
  4. 4. Structure-activity relationship <ul><li>NT fits receptor site </li></ul><ul><ul><ul><li>key & lock </li></ul></ul></ul><ul><li>Change structure of drug... </li></ul><ul><ul><li>change its affinity </li></ul></ul><ul><ul><ul><li>increase or decrease </li></ul></ul></ul><ul><ul><li>may bind to different receptor </li></ul></ul><ul><li>Behavior mediated by synaptic activity </li></ul><ul><ul><li>most drugs act at synapse ~ </li></ul></ul>
  5. 5. Acetylcholine - ACh <ul><li>Most abundant NT in Peripheral N.S. </li></ul><ul><ul><li>also found in Central N.S. </li></ul></ul><ul><ul><li>Precursor = choline </li></ul></ul><ul><li>Degraded by acetylcholinesterase- </li></ul><ul><ul><li>AChE </li></ul></ul><ul><li>Nicotinic receptor – ionotropic </li></ul><ul><ul><li>*Nonselective ionophores </li></ul></ul><ul><ul><li>*Requires 2 Ach for activation </li></ul></ul><ul><li>Muscarinic receptor - metabotropic ~ </li></ul>
  6. 6. ACh - Distribution <ul><li>Peripheral N.S. </li></ul><ul><li>Excites somatic muscle </li></ul><ul><li>Autonomic NS </li></ul><ul><ul><li>Ganglia </li></ul></ul><ul><ul><li>Parasympathetic NS Neuroeffector junction </li></ul></ul><ul><li>Central N.S. - widespread </li></ul><ul><ul><li>Hippocampus </li></ul></ul><ul><ul><li>Hypothalamus ~ </li></ul></ul>
  7. 7. ACh N M AChE AChE Botulinum toxin BWSV curare atropine A
  8. 8. Excitatory Amino Acids: Glutamate <ul><li>Primary NT in CNS excitatory neurons </li></ul><ul><ul><li>Nonessential amino acids </li></ul></ul><ul><li>Synthesis </li></ul><ul><ul><li>Precursor glutamine from astroglia </li></ul></ul><ul><li>Termination </li></ul><ul><ul><li>presynaptic & glial reuptake ~ </li></ul></ul>
  9. 9. Excitatory Amino Acids: Glutamate <ul><li>Receptor subtypes </li></ul><ul><ul><li>Metabotropic (mGlu-R) </li></ul></ul><ul><ul><ul><li>Inhibition of Na + & Ca ++ channels </li></ul></ul></ul><ul><ul><li>Ionotropic: NMDA-R; AMPA-R </li></ul></ul><ul><ul><ul><li>nonselective </li></ul></ul></ul><ul><li>Excitotoxicity </li></ul><ul><ul><li>Following brain injury </li></ul></ul><ul><ul><li>Elevated Glu activity </li></ul></ul><ul><li>Aspartate ~ </li></ul>
  10. 10. Inhibitory Amino Acids: Glycine <ul><li>Primarily spinal cord </li></ul><ul><li>Cl - channels </li></ul><ul><li>Strychnine is antagonist ~ </li></ul>
  11. 11. Inhibitory Amino Acids: GABA <ul><li>Gamma-aminobutyric acid - GABAergic </li></ul><ul><li>Major NT in brain inhibitory systems </li></ul><ul><li>Receptor subtypes </li></ul><ul><ul><li>GABA A / GABA C ionotropic Cl- channel </li></ul></ul><ul><ul><li>GABA B - metabotropic K+ channels </li></ul></ul><ul><li>Precursor = glutamate ~ </li></ul>
  12. 12. Biogenic Amines (Monamines) <ul><li>Amino acid precursors </li></ul><ul><ul><li>single amine group </li></ul></ul><ul><li>2 groups </li></ul><ul><ul><li>Catecholamines - catechol ring </li></ul></ul><ul><ul><ul><li>Tyrosine precursor </li></ul></ul></ul><ul><ul><li>Indolamine - indole ring </li></ul></ul><ul><ul><ul><li>Tryptophan precursor </li></ul></ul></ul><ul><li>Affected by many of same drugs ~ </li></ul>
  13. 13. Monamines <ul><li>Catecholamines </li></ul><ul><li>Dopamine - DA </li></ul><ul><ul><li>Dopaminergic </li></ul></ul><ul><li>Norepinephrine - NE </li></ul><ul><ul><li>Noradrenergic </li></ul></ul><ul><li>Epinephrine - E </li></ul><ul><ul><li>Adrenergic </li></ul></ul><ul><li>Indolamines </li></ul><ul><li>Serotonin - 5-HT </li></ul><ul><ul><li>Serotonergic </li></ul></ul>
  14. 14. Monamines <ul><li>Terminated by... </li></ul><ul><ul><li>reuptake </li></ul></ul><ul><ul><li>monoamine oxidase - MAO </li></ul></ul><ul><ul><li>catechol-O-methyltranferase - COMT </li></ul></ul><ul><ul><li>also in liver </li></ul></ul><ul><li>Reserpine  leaky vesicles </li></ul><ul><ul><li>depletes monoamines ~ </li></ul></ul>
  15. 15. A Monoamines MAO MAO COMT Reserpine
  16. 16. Dopamine <ul><li>Only in central nervous system </li></ul><ul><ul><li>mostly inhibitory systems </li></ul></ul><ul><li>Reward </li></ul><ul><li>Schizophrenia </li></ul><ul><li>Movement </li></ul><ul><ul><li>Nigrostriatal Pathway </li></ul></ul><ul><li>At least 5 DA-R types: D1, D2, etc. ~ </li></ul>
  17. 17. Norepinephrine <ul><li>Peripheral N.S. </li></ul><ul><ul><li>Sympathetic neuroeffector junction </li></ul></ul><ul><ul><li>Adrenal glands </li></ul></ul><ul><li>Central N.S. </li></ul><ul><ul><li>Hypothalamus </li></ul></ul><ul><ul><li>Locus coeruleus </li></ul></ul><ul><li>Alpha & Beta receptor subtypes </li></ul><ul><ul><li>NE  & NE  ~ </li></ul></ul>
  18. 18. Serotonin <ul><li>NOT a catecholamine </li></ul><ul><li>Peripheral </li></ul><ul><ul><li>98% in blood & smooth muscle </li></ul></ul><ul><li>Central N.S. </li></ul><ul><ul><li>Raphe nucleus </li></ul></ul><ul><ul><li>Hypothalamus </li></ul></ul><ul><li>R subtypes: 5HT 1 & 5HT 2 ~ </li></ul>
  19. 19. Neuropeptide <ul><li>Chains of amino acids </li></ul><ul><ul><li>Synthesis in soma </li></ul></ul><ul><li>Often neuromodulators </li></ul><ul><ul><li>alters sensitivity of neurons </li></ul></ul><ul><ul><li>slower, longer-lasting effects </li></ul></ul><ul><li>Substance P - pain signaling </li></ul><ul><li>Endorphins - analgesia, euphoria ~ </li></ul>
  20. 20. Endorphins <ul><li>Opioids </li></ul><ul><ul><li>Dynorphin </li></ul></ul><ul><ul><li>met-enkephalin </li></ul></ul><ul><ul><li>leu-enkephalin </li></ul></ul><ul><ul><li>Beta-endorphin </li></ul></ul><ul><li>Receptor subtypes: </li></ul><ul><ul><li>mu 1 , mu 2 , kappa, delta ~ </li></ul></ul>
  21. 21. Unconventional NTs <ul><li>Retrograde messengers </li></ul><ul><ul><li>Ca ++ -dependent </li></ul></ul><ul><ul><li>Not stored in vesicles </li></ul></ul><ul><li>Nitric Oxide - It’s a gas </li></ul><ul><ul><li>Synthesis on demand by NO synthase </li></ul></ul><ul><ul><li>LTP ~ </li></ul></ul>
  22. 22. Unconventional NTs <ul><li>Endocannabinoids </li></ul><ul><ul><li>Anandamide </li></ul></ul><ul><ul><li>2 - AG </li></ul></ul><ul><ul><li>Inhibits presynaptic GABA release </li></ul></ul><ul><ul><li>Synthesis by enzymatic degradation of membrane ~ </li></ul></ul>

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