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~BN13 neurotransmitters.ppt

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