Reuptake from synaptic cleft into presynaptic neurons

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Reuptake from synaptic cleft into presynaptic neurons Monoamine oxidase (MAO)- enzyme that breaks down monoamines intranueronally 2 isoforms: MAO-A & MAO-B Both forms break down DA, but MAO-B found in dopaminergic terminals buttons Also in blood where it deactivates amines thereby preventing dangerous increases in blood pressure Catechol-O-methyltransferase (COMT)- enzyme that breaks down catecholamines extraneuronally Minor factor in catecholamine deactivation
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Major SMT’s Monoamines Dopamine (DA) Norepinephrine (NE) Epinephrine (Epi) Histamine Serotonin or 5- Hydroxytryptamine (5- HT) Quarternary Amine Acetylcholine (Ach) Purines Adenosine ATP Amino Acids Gamma Aminobutyric Acid (GABA) Glycine Glutamate Aspartate
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Large Molecule (Peptide) Neurotransmitters Peptides are usually broken down from large molecules called polypeptides by specific enzymes Peptides-chains of amino acids linked by peptide bonds The polypeptide are synthesized in the rough ER & then it is broken down into propeptides Propeptides migrate to the Golgi where they are packaged into large dense core vesicles (LDCV) which migrate to the axon hillock LDCV’s are actively transported to the butons bypassing vericosities LMT’s are formed en route in the LDCV’s by endoproteases which break down the propeptide into peptides that will be released Release is frequency modulated in that low firing (low frequency of AP’s) results in no release Above a threshold the more AP’s the more LDCV’s get released No reuptake or recycling, peptides are broken down upon release Broken down by pepsidases (non specific)
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Figure 2.25 The preprohormone
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An Example: Pro-opiomelanocortin (POMC)
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LMT’s Many but the best known Substance P Neurokinin A & B Edogenous opioids Beta endorphin Enkephalin Dynorphin Cholecystokinin (CCK)
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SMT & LMT Synthesis & Storage
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Differences in SMT & LMT Reuptake by presynaptic neuron SMT yes LMT no Release with AP arrival SMT-quantal LMT-frequency modulated Broken down by enzymes SMT-neurotransmitter specific LMT-non-specific pepsidases SMT & LMT are co-localized 2 types of signaling SMT alone SMT + LMT Colocalization Ach with Sub P, Galanin DA with enkephalin, CCK, neurotensin GABA with somatostatin, Motilin, neuropeptide Y NE with enkephalin, vasopressin, galanin 5-HT with enkephalin, sub P, thyrotropin releasing hormone
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Comparison Diagram comparing classic neurotransmitters (LMT) and Neuropeptides (SMT)
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Receptors Types of Receptors Ionotropic Ligand-gated ion channel Metabotropic G-protein coupled receptor (GPCR) Enzymatic Protein kinase or phosphatase Cytosolic Hormone receptors
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Types of Receptors
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Ionotropic Receptors Agoinsts binding opens ion channels Influx of Na+ or Ca++ cause membrane depolarization (EPSP) Efflux of K+ or influx of Cl- cause membrane hyperpolarization (IPSP) Response time between 1-5ms
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GPCR Agonist binding to receptors causes them to couple to a transducer (G-protein) Affects one or more effectors (enzymes) Catalyze precursors into second messengers Can affect Ion channels Pumps Metabolic activity
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