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Neurotransmitter. #2 group (Ajou, Sogang Univ.). An Bum-Chu, Lee Kyung-Bun. ACADEMYIC CONFERENCE OF LIFE SCIENCE. Content. Introduction Neurotransmitter Definition, synthesis & storage, Release, Recovery & degradation, discovery Receptor
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Neurotransmitter #2 group (Ajou, Sogang Univ.) An Bum-Chu, Lee Kyung-Bun ACADEMYIC CONFERENCE OF LIFE SCIENCE
Content • Introduction • Neurotransmitter • Definition, synthesis & storage, Release, Recovery & degradation, discovery • Receptor • Receptor type (transmitter-gated ion channel, G-protein coupled receptor) • AChR, GABAAR, Dopamine receptor, Glutamate receptor, Opioid receptor • Neuropharmacology • Agonist and Antagonist • Cocaine & Amphetamine, Caffeine, opioid, nicotine, alcohol
Introduction • Why should we study neurotransmitter about addiction? • How will we study neurotransmitter about addiction?
Definition • The molecule must be synthesized and stored in the presynaptic neuron. • The molecule must be released by the presynaptic axon terminal upon stimulation. • The molecule, when experimentally applied, must produce a response in the postsynaptic cell that mimics the response produced by the release of neurotransmitter from the presynaptic neuron.
Major neurotransmitter AMINO ACID AMINE PEPTIDE GABA acetylcoline cholestokinin glutamate Dopamine dynorphin glycine epinephrine enkephalines histamine NAAG norepinephrine Neuropeptide Y serotonine somatostatin Substance P Thyropin-releasing hormone Vasoactive intestinal polypeptide Classification • Amino acid • Amine • Peptide
Synthesis & Storage • Amino acid & Amine • Peptide
Synthesis & Storage • Colinergic neuron • Catecholaminergic neuron • Serotoninergic neuron • Amino acidergic neuron
Release • Arrival of AP • Ca2+ channel open (voltage dependent) • Ca2+ influx • Exocytosis (synaptic vesicle)
Recovery & Degradation • Diffusion • Reuptake • Presynapse transport & glia transport • Degradation • Degradation by enzyme AChE acetylcolin Acetate + choline
Discovery • Immuno - cytochemistry • In situ hybridization
Receptor • Receptor type • AChR (Acetylcoline receptor) • GABAA receptor • Dopamine receptor • Glutamate receptor • Opioid receptor
Receptor Type • Transmitter-gated ion channel • IPSP (inhibitatory postsynaptic potential) • EPSP (excitatory postsynaptic potential) • G-protein coupled receptor • Shortcut pathway • Second messenger cascade
(acetylcolin receptor) AChR • nAChR • Skeletal muscle • Transmitter-gated ion channel • 4 subunit & pentamer • mAChR • Cardiac muscle • G protein-coupled receptor • 4 subtype (m1, m2, m3, m4)
GABAA Receptor • Transmitter-gated ion channel • Cl- ion influx (IPSP)
Dopamine Receptor • G-protein coupled receptor • D1-like family (D1, D5) • D2-like family (D2-D2L · D2S, D3, D4)
Glutamate Receptor • AMPA, NMDA, kainate • Transmitter-gated ion channel • Mechanism
Opioid Receptor • Antinociception • G-protein coupled receptor • Subtype • μ (μ1·μ2), δ(δ1·δ2), κ(κ1·κ2·κ3)
Neuropharmacology • Antagonist & agonist • Action of addictive drugs • Coanine & amphetamine • Caffeine • Opioites • Nicotine • Alcohol
Action of addictive drugs • drug : imitation or inhibition of secretion of specific neurotransmitter • antagonist Blocking of specific neurotransmitter • agonist Imitation or increase of neurotransmitter • The ways the drug can affect the synaptic transmission
Action of addictive drugs • Dopamine-neurotransmitter of CNS • synthesis, storage, release • actions of dopamine • Dopaminergic nigro-neostriatal pathway • Mesolimbic dopaminergic pathway • Tubo-infundidular system
Cocaine & Amphetamine • Mechanism • Cocaine and amphetamine → binding to dopamine reuptake trandporter → inhibition of dopamine reuptake→ accumulation of dopamine in synapse → stimulation of receptor → incresed dopamine activity • Actions of cocaine& amphetamine : temporary • Autoreceptor • Flash (add cocaine, without cocaine) • Amphetame-powerfully dopamine releases -mentaliy, physically
Inhibition of dopamine reuptake • Other drug ex.cocaine, amphetamine, domperidone
Caffeine • Caffeine • action : heart rate increase, blood vessel constriction , headache • Inhibition of adenosine • adenosine : inhibition of dopamine release • As a result, increase of dopamine release
Opiates • Morphine, heroin • endolphin: neurotransmitter released from brain • endolphin opiates → receptor → excite of periaqueductal gray area → decreased secretion of P substance → decreased pain
Nicotine • Chemical in cigarette • nicotinic receptor(acethycholine receptor) blocking • Binding to receptor that increase the sectretion of doapmine in nucleus accumbens → reinforce • Catecholamine release → rised blood pressure, perspiration
Alcohol • Disfunction of recognition (inference, memory etc) • Influx inhibition of Na+→prevention of nerve system • Decrease of serotonin, activation of GABA receptor