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Lecture 8+9 - Neurotransmitters

Lecture 8+9 - Neurotransmitters - Neurotransmi,ers In the...

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Neurotransmi,ers In the 60's, people took acid to make the world weird. Now the world is weird and people take Prozac to make it normal.
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Processes’Involved’in’Neurotransmission’ Precursors ’(ge6ng’the’raw’materials)’ Biosynthesis ’(making’the’NTs)’ Storage ’(vesicles’-’Golgi’bodies)’ Transport ’(neuroflaments’and’microtubules)’ Docking Influx of Ca ++ Vesicle movement Exocytosis —’(Fusion’and’release)’ Crossing synapAc gap Binding ’postsynapDc’receptors’ Reuptake ’mechanisms’to’recover’NTs’ DeacAvaAon
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Categories of NTs Amino’Acids’ Glutamate (Glu) GABA Biogenic’Amines’ Quaternary’Amines’ Acetylcholine (Ach) Monoamines’ • Catecholamines’ Dopamine (DA) Norepinephrine (NE) • Indolamines’ Serotonin (5-HT) NeuropepDdes’ Opioid’PepDdes’ Enkephalins Endorphins Dynorphins Others’(e.g.’lipids,’nucleosides)’
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Receptors GeneDcally-coded’proteins’embedded’ in’cell’membrane’ GaDng’ Ligand-gated ’ -’Stretch-gated’ Voltage-gated’ Efects’ Ionotropic’ Metabotropic’ LocaDon’ PostsynapDc’ PresynapDc’ • Heteroreceptor’ • Autoreceptor’ ionotropic metabotropic
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Ionotropic Receptors 1. Work’very’fast;’important’role’in’fast’neurotransmission’ 2. Each’is’made’of’several’subunits’(together’form’the’complete’receptor)’ 3. At’center’of’receptors’is’channel’or’pore’to’allow’flow’of’neurotransmiZer’ 4. At’rest’-’receptor’channels’is’closed’ 5. When’neurotransmiZer’bind’--’channel’immediately’opens’ 6. When’ligand’leaves’binding’site’--’channel’quickly’closes’
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Metabotropic Receptors 1. Work’more’slowly’than’ionotropic’receptors’ 2. Though’it’takes’longer’for’postsynapic’cell’to’respond,’response’is’ somewhat’longer-lasDng’ 3. Comprise’a’single’protein’subunit,’winding’back-and-forth’through’cell’ membrane’seven’Dmes’( transmembrane domains )’ 4. They’do’not’possess’a’channel’or’pore’
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Theory of Drug Ac<on Emil Fischer ` s b Lock and Key Hypothesis (1890) ü Every’ b lock ` ’has’its’own’ b key ` ü If’the’ b key ` ’is’not’precise,’the’ b lock ` ’does’not’open’ ü The’ b drug ` ’is’the’key’that’has’to’Ft’the’target’speciFcally’and’ producDvely’
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Theory of Drug Ac<on Corollary of b Lock & Key ` Hypothesis ü Does’not’explain’why’some’ b keys ` ’open’doors’par±ally?’……’e.g.,’par±al’agonists’or’ antagonists’ O O O H O OH
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Theory of Drug Ac<on Daniel Koshland ` s b Induced-Fit Hypothesis (1958) ü At’least’two’steps’……’step’1’is’iniDal’binding’and’step’2’is’a’ change’in’structure’of’the’receptor’(and/or’drug)’ ü Receptor’is’flexible!’……’can’wrap’around’the’drug’
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Lecture 8+9 - Neurotransmitters - Neurotransmi,ers In the...

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