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SC BIOL 460 - Monoamine Neurotransmitters

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Outline of LectureI. Monoamine Neurotransmitters and their mechanismsII. Anatomy of the BrainIII. What each monoamine neurotransmitter doesMonoamine Neurotransmitters (NTMs)-(released at synapse)BIOL 460 1st Edition Lecture 1 Outline of LectureI. Monoamine Neurotransmitters and their mechanismsII. Anatomy of the BrainIII. What each monoamine neurotransmitter doesMonoamine Neurotransmitters (NTMs)-(released at synapse)1. Contain an amino group connected to an aromatic ring by a 2-carbon chain2. Includes:a. Serotonin- derived from tryptophanb. Catecholamines- derived from tyrosinei. Dopamineii. Epinephrine iii. Norepinephrineiv. Catechol group → aromatic ring with to hydroxyl groups 3. When monoamine NTMS are released, they must be removed or destroyed soreceptors aren’t always ona. One way→ Monoamine oxidase (MAO)- in cytoplasm of terminal bouton b. Transport proteins in terminal boutonc. Reuptake of monoamines into cytoplasm via facilitated diffusion, broken down by MAOd. Several drugs prevent dopamine reuptake by blocking the transport protein (cocaine)4. Catecholamine NTMs can also be inactivated in the cytoplasm of post-synaptic cellsa. Transporter takes catecholamine up into cellb. Inactivated by catechol-o-methyl transferase (COMT)  adds methyl group5. Mechanism of action (see figure 7.31) *possible essay questiona. monoamine bonds to receptorb. G protein is used as second messengerc. Alpha subunit turns on adenylate cyclase, converting ATP to cyclic adenosine monophosphate (cAMP) and pyrophosphate (PO4-PO4)d. cAMP is a very common 2nd messengere. cAMP activates protein kinase, which add a phosphate to a protein (phosphorylates the protein)i. phosphates are strongly polarii. alters protein conformation, makes protein active (can be an ion channel or enzyme)1. kinase is inactive because kinase is a dimer (2 parts- regulatory subunit: more affinity for cAMP than catalytic part of protein kinase)f. g-protein turns itself offg. monoamine inactivates by MAO or COMT (if catecholamine)h. cAMP broken down by phosphodiesterasei. protein phosphatases reverse action of protein kinases6. What monoamine NTMs doa. Brain anatomy of subphylum vertebrata b. Five regions of the brain (front to back)i. Telencephalon 1. Largest part in mammals and birds2. Cerebral hemispheres (cerebrum, limbic system)3. Cerebral cortex a. Layer of gray matter on surface of cerebral hemisphereb. On outside= more surface area c. White matter insideii. Diencephalon 1. Neck region 2. Top- epithalamus, pineal gland 3. Middle/walls- thalamusa. Relay station b. Sends signals to telencephalon4. Bottom- hypothalamus a. Contains basal nuclei b. Autonomic nervous system c. Pituitary gland- dangle from bottomiii. Mesencephalon- “mid-brain”1. Roof- tectum, vision in fishes2. Floor- tegmentum iv. Metencephlaon (unconscious control)1. Cerebellum- “mid-cerebrum”a. Little brain b. Refines movement of skeletal musclec. Gray matter on outside d. White matter on inside- arbor vitae2. Pons- fiber tract- convey info back and forth from cerebrum to cerebelluma. Relay station b. Spinal cord → telencephalon c. Contains Raphe nuclei v. Myelencephalon1. Medulla oblongata- brainstem 2. Centers (controls ANS)a. Respiratory centerb. Cardiac center c. Serotonin i. Synthesized from tryptophan ii. Contains indole ring instead of catechol groupiii. LSD is an agonist for serotonin (also has indole group)1. Affects mood and emotion2. Can learn about endogenous NTMs by discovering agonists drugs and poisons iv. Serotonergic neurons- receptors that bond to serotonin1. Raphe nucleus in pons2. Sends projections (axons) to telencephalon v. Affect mood, behavior, sleep, appetite, and circulation 1. Lots of effects because there are several types of serotonin receptors2. Each receptor has its own effect3. Migraine are caused by vasoconstriction of brain arteriesvi. Biochemistry of depression 1. Zoloft, Paxil, Prozac, Luvox → SSRIs (serotonin specific reuptake inhibitors)a. Inhibits reuptake of serotonin into terminal bouton; extends effect of serotonin release d. Dopamine i. tyrosine→ DOPA→ dopamine ii. dopaminergic neurons1. nigrostriatial dopamine system a. cell bodies in substantia nigra i. nigra= blackii. named after dark color of substantia nigra iii. dark because of melanin pigment produced as byproduct of dopamine synthesisb. project into basal nuclei of telencephalonc. one projection/axon is corpus striatum (nigrostriatial dopamine system)d. involved in initiation of skeletal muscle movement e. Parkinson’s Disease i. Dopaminergic neurons degenerate ii. Treatment- L-DOPA, precursor to dopamine that can cross blood brain barrier iii. Fatal disease iv. Also given MAO and COMT inhibitors to prevent dopamine


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