neurotransmitters.ppt 4
DESCRIPTION
NEUROTRANSMITERTRANSCRIPT
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Neurotransmitters
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Neurotransmitter Criteria1. IdentitySubstance must be found in neurons
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Neurotransmitter Criteria1. Identity2. SynthesisCell has precursors and enzymes necessary for synthesis
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Neurotransmitter Criteria1. Identity2. Synthesis3. ReleaseMust be released from terminals; (collect substance from cleft after nerve stimulation)
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Neurotransmitter Criteria1. Identity2. Synthesis3. Release4. ReceptorsCross desensitization between substance and suspected n.t.Blockade of n.t. action by receptor antagonistsApplicaton of suspected n.t. mimics action of nerve stimulation
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Neurotransmitter Criteria1. Identity2. Synthesis3. Release4. Receptors5. InactivationInactivation mechanism enzymatic degradation reuptake
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Neurotransmitter Criteria1. Identity2. Synthesis3. Release4. Receptors5. Inactivation6. PharmacologySame effect on ion channels; p.s.p.s have same reversal potentialsSame effect on membrane resistance and potentialApplied substances must be effective in physiological concentrationsInhibition of degrading enzyme prolongs action of both
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Neurotransmitter Criteria1. Identity2. Synthesis3. Release4. Receptors5. Inactivation6. Pharmacology
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Acetylcholine SynthesisDegradation+ CoA
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Chemicals that Acton ACh Systemsblack widow spider venomstimulates release of AChbotulinum toxinblocks release of AChcurareblocks ACh nicotinic receptorsinsecticidesAChE inhibitorsatropine as antidoteblocks muscarinic receptors
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Clinical Aspectsof ACh SystemsAlzheimers diseaseloss of ACh neurons inthe basal nucleus of MeynertAriceptACh agonist
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Monoaminessingle amine (NH2) groupCatecholamines (CAs)dopamine (DA)norepinephrine (NE, noradrenaline)epinephrine (EPI, adrenaline)Indoleaminesserotonin (5-hydroxy tryptamine, 5-HT)
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Catecholamine synthesis
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Serotonin synthesis
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Dopamine Systems
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Norepinephrine Systems
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SystemsSerotonin
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Characteristics of Monoaminergic SystemsDiffuse distribution of targetsFine, unmyelinated axonsMetabotropic synapses
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Functions of Monaminergic SystemsState phenomenasleep and arousalhungermood
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Amino Acid TransmittersExcitatory Amino AcidInhibitory Amino AcidsGlutamic Acid, or GlutamateGamma Aminobutyric Acid (GABA)Glycine
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Glutamate Receptor Subtypes
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NMDA receptor binding sites
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http://www.sumanasinc.com/webcontent/anisamples/neurobiology/receptors.html
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Glutamatenon-NMDA receptorsNMDA receptorsNa+ channelsopenCa2+ channelsopen(Mg2+ blockade)depolarizationremovesblockadeCa2+ enterswhen Mg2+is removedCa2+dependentK+ channels openrepolarizationpostsynapticeffects(learning)reinstates blockade
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abcNon-NMDA Na+ channels open, Na+enters and depolarizes membraneb. Mg2+ blockade of NMDA Ca2+ channelsremoved by membrane depolarization; Ca2+ entersCa2+ dependent K+ channels open;membrane repolarizedd. Mg2+ blockade reinstatedd
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GABA receptor binding sites
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PeptideNeurotransmitters(Often serve hormonal functions as well)Substance P (P for Peptide)Principal somatosensory transmitterFirst peptide transmitter discoveredGut hormonese.g. angiotensin neuropeptide Y cholecystokininReleasing factors for hormonese.g. tryrotropin releasing hormone somatotrophin, somatostatin corticotropinOpiatesEnkephalins, Endorphins
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Diffusible GasesNitric Oxide (NO)Carbon Monoxide (CO)HemeCO + biliverdinHeme Oxygenase
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Functions of Diffusible GasNeurotransmittersregulate blood flowcerebralperipheral (e.g. penis)retrograde messengerHebbs postulate of learning
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Summary of Neurotransmitters
Small Molecule Neurotransmitter SubstancesAcetylcholine (ACh)Dopamine (DA)Norepinephrine (NE)Serotonin (5-HT)HistamineEpinephrine
Amino AcidsGamma-aminobutyric acid (GABA)GlycineGlutamateAspartate
Neuroactive Peptides - partial listbradykininbeta-endorphinbombesincalcitonincholecystokininenkephalindynorphininsulingastrinsubstance Pneurotensinglucagonsecretinsomatostatinmotilinvasopressinoxytocinprolactinthyrotropinangiotensin IIsleep peptidesgalaninneuropeptide Ythyrotropin-releasing hormonegonadotropnin-releasing hormonegrowth hormone-releasing hormoneluteinizing hormonevasoactive intestinal peptide
Soluble GasesNitric Oxide (NO)Carbon Monoxide