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Neurotransmitter #2 group (Ajou, Sogang Univ.) An Bum-Chu, Lee Kyung-Bun ACADEMYIC CONFERENCE OF LIFE SCIENCE Content Introduction Neurotransmitter Receptor Definition, synthesis & storage, Release, Recovery & degradation, discovery 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. Classification Amino acid Amine Peptide 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 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 acetylcolin AChE Acetate + choline Discovery Immuno cytochemistry In situ hybridization Receptor Receptor AChR type (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) nAChR Skeletal muscle Transmitter-gated ion channel 4 subunit & pentamer mAChR Cardiac muscle G protein-coupled receptor 4 subtype (m1, m2, m3, m4) AChR 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 synthesis, storage, release actions of dopamine of CNS Dopaminergic nigro-neostriatal pathway Mesolimbic dopaminergic pathway Tubo-infundidular system Mesolimbic dopaminergic reward 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 Pain pathway pathway of analgesia suppression 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 nicotinic receptor and its action Alcohol Disfunction of recognition (inference, memory etc) Influx inhibition of Na+ → prevention of nerve system Decrease of serotonin, activation of GABA receptor