Term
| Primary excitatory neurotransmitter in the mammalian brain |
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Definition
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Term
| Glutamatergic synapses are |
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Definition
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Term
| Principal outflow neurons from the brain region are predominantly |
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Definition
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Term
| Two neurotransmitters that do not cross blood brain barrier |
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Definition
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Term
| Minor pathway of glutamate synthesis |
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Definition
| NH+ + alpha keto glu + NADPH = glu +H20 +NADP |
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Term
| Enzyme that catalyzes the minor pathway of glu synth |
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Definition
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Term
| Major pathway of glutamate synth |
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Definition
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Term
| Enzyme of major pathway of glu synth |
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Definition
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Term
| Where in neurons is glnase primarily found |
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Definition
| in the omm of the mitochondria |
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Term
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Definition
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Term
| Glu release from synaptic vesicles is a |
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Definition
| calcium dependent process |
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Term
| Glu transport from cyto to vesicle requires |
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Definition
| energy b/c going up [] gradient |
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Term
| Transporters responsible for glu transport into vesicle |
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Definition
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Term
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Definition
| receptor for the neurotransmitter released by that neuron |
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Term
| Glu release is regulated by |
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Definition
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Term
| What can inhibit Glu release? |
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Definition
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Term
| How does glu binding to autoreceptors lower glu release |
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Definition
| reduce sensitivity of the release process to calcium |
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Term
| An autoreceptor for glu is activated by |
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Definition
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Term
| What receptors act as autoreceptors for Glu? |
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Definition
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Term
| Major mechanism for Glu inactivation in the synapse? |
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Definition
| Uptake through PM transporters by astrocytes |
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Term
| What are the glu transporters found on astrocytes |
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Definition
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Term
| EAATs are primarily expressed where |
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Definition
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Term
| What is the mechanism by which EAATs work |
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Definition
| Secondary active transport by co-transport w/ sodium |
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Term
| Steps in the Glu/Gln shuttle |
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Definition
1.Glu accumulated by astrocyte is converted to gln
2.Gln is released and taken up by neurons
3.In neurons gln is converted to glu and repackaged in vesicles for release |
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Term
| Enzyme that turns Glu to Gln |
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Definition
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Term
| Why do we have to control Glu levels? |
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Definition
| Glu in increased quantities is toxic. |
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Term
| Two types of glu receptor categories |
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Definition
1. Ionotrophic
2. Metabotrophic |
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Term
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Definition
| ligand gated ion channels |
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Term
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Definition
| G protein coupled receptors |
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Term
| 2 categories of Glu ionotrophic receptor channels |
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Definition
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Term
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Definition
| conduct sodium and potassium but mostly sodium and create slow excitatory bumps (so can trigger AP if enough of them to depolarize the cell) |
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Term
| Two types of non-NMDA channels |
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Definition
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Term
| What ions do NMDA channels conduct |
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Definition
| calcium, sodium and potassium but mostly Ca-big pipe for Ca |
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Term
| What does NMDA need to open |
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Definition
1.glycine cofactor
2.depolarization by non-NMDA to remove Mg plug
3. glu binding |
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Term
| What blocks NMDA channels at resting potential |
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Definition
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Term
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Definition
| slow kinetics ie slow to open or close good b/c too much Ca is toxic |
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Term
| What are the metabotropic receptors for glu |
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Definition
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Term
| What do Glu metabotropic receptors post synaptically do |
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Definition
| activate couplers (g-proteins) to open ion channels or have intracellular Ca release |
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Term
| What do Glu metabotropic receptors do presynaptically |
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Definition
| function via g-proteins to inhibit further glu release by reducing the neurons Ca sensitivity |
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Term
| Glu receptors are found primarily on... |
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Definition
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Term
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Definition
| vast majority of fast transmission in the brain which is largely Na currents |
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Term
| AMPA receptors function to |
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Definition
| move membrane potential toward threshold |
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Term
| Primary role of NMDA receptors |
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Definition
| increase intracellular Ca rather than depolarization which plays a role in activity dependent synaptic plasticity |
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Term
| Injections of AMPA agonists cause |
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Definition
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Term
| Excessive stimulation of glutamatergic pathways causes |
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Definition
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Term
| Diseases that involve overactive glutamatergic systems |
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Definition
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Term
| Excitotoxicity results from |
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Definition
| prolonged lack of Oxygen or glu |
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Term
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Definition
| too much intracellular calcium |
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Term
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Definition
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Term
| Where are Noradrenergic neurons found primarily? |
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Definition
| medulla oblongata, pons, and midbrain |
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Term
| Medulla oblongata pons and midbrain are called the |
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Definition
| reticular activating system |
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Term
| reticular activating system function |
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Definition
1. important in arousal (wakefulness)
2. regulation of autonomic functions like breathing and BP |
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Term
| what is the precursor of NE |
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Definition
|
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Term
| can tyrosine cross the BBB |
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Definition
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Term
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Definition
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Term
| Tyrosine is converted to...by... |
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Definition
| DOPA by tyrosine hydroxylase |
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Term
| DOPA is converted to...by.... |
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Definition
| dopamine by DOPA decarboxylase |
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Term
| dopamine is converted to...by... |
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Definition
| NE by dopamine beta hydroxylase |
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Term
| Primary regulation of NE synth is via |
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Definition
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Term
| What is the rate limiting step for NE synthesis |
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Definition
| TH conversion of tyr to DOPA |
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Term
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Definition
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Term
| Essential cofactor for TH |
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Definition
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Term
| Short term regulation of TH activity occurs generally by |
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Definition
1.phosphorylation at 4 different serine residues
2.end product inhibition of BH4 |
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Term
| How does end-product inhibition of NE synthesis work |
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Definition
| NE [] becomes so high in vesicles it begins to leak out and free NE inhibits BH4 binding to TH |
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Term
| Long term regulation of TH |
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Definition
| occurs via new protein synthesis of TH |
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Term
| TH is saturated normally w/ tyr but not |
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Definition
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Term
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Definition
| inhibits BH4 binding to TH |
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Term
| TH affinity for BH4 is regulated by |
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Definition
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Term
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Definition
| high TH activity and vice versa |
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Term
| Increased phosphoylation of TH means |
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Definition
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Term
| TH activity is helped by increased Ca levels b/c |
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Definition
1. increased Ca means increased neuronal activity so needs more NE
2. Ca activates kinases that can in turn activate TH |
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Term
| What kinases phosphorylate TH? |
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Definition
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Term
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Definition
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Term
| Adenylate cyclase is regulated by |
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Definition
| a g-protein so regulates cAMP levels as well |
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Term
| How do NE autoreceptors work? |
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Definition
| Inhibit cAMP so decrease PKA activity so decreased phosphorylation so decrease TH affinity for BH4 so decreased TH activity |
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Term
| What activates CAM kinase |
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Definition
| increased intracellular calcium |
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Term
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Definition
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Term
| What initially activates G-protein cascade responsible for PKA activation |
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Definition
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Term
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Definition
| vesicles with dopamine beta-hydroxylase-dopamine is taken into the vesicle and last step occurs there |
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Term
| What transports dopamine into vesicles |
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Definition
| Vesicular monoamine transporters VMAT |
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Term
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Definition
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Term
| 3 mechanisms for NE release |
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Definition
1. Ca dependent exocytosis of vesicles like glu
2.reversal of plasma membrane transporters
3.dendritic release that is not ca dependent |
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Term
| Non calcium dependent ways of NE release |
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Definition
1. reversal of plasma membrane transporters
2. dendritic release |
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Term
| How does reversal of plasma membrane transporter mediated NE release occur |
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Definition
| increase concentration of NE inside the presynaptic neuron increases the [] gradient until NE is pushed out |
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Term
| Mechanisms that raise the NE [] for reversal of PM transporter mediated NE release |
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Definition
| 1. reuptake of NE into presynaptic terminal 2. reversal of VMAT2 due to [] gradient |
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Term
| Two types of NE autoreceptors |
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Definition
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Term
| alpha2 NE autoreceptor function |
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Definition
| inhibits release by decreasing calcium sensitivity (-feedback loop) |
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Term
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Definition
| increases release of NE by increasing cAMP and Ca (feed foward regulation) |
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Term
| Release of NE modulated by |
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Definition
| presynaptic autoreceptors |
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Term
| Two types of NE regulation |
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Definition
1.release (autoreceptors)
2.synthesis |
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Term
| All transmitters can be inactivated by |
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Definition
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Term
| Most important NE inactivation |
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Definition
| reuptake by presynaptic neuron NOT astrocytic |
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Term
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Definition
1. High affinity carrier proteins like Noradrenergenic transporter (NAT)
2.Sodium co-transporter |
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Term
| Fate of intracellular NE in reuptake |
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Definition
1. repackaged for release
2. degraded by enzymes |
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Term
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Definition
1. Monoamine oxidase MAO
2. Catecho-O-methyl-transferase COMT |
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Term
| What are the two forms of MAO |
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Definition
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Term
| What form of MAO is found in the brain |
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Definition
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Term
| How does MAO inactivate NE |
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Definition
| deaminates norepinephrine |
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Term
| What do MAO and COMT act on besides NE |
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Definition
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Term
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Definition
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Term
| How does COMT deactivate NE |
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Definition
| transfers a methyl group from SAM to the NE |
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Term
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Definition
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Term
| NE binds to what type of receptors generally |
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Definition
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Term
| 2 types of adrenergic receptors |
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Definition
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Term
| What binds alpha receptors better NE or epi |
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Definition
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Term
| Two types of alpha receptors |
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Definition
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Term
| Where are alpha 1 receptors |
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Definition
| predominantly post-synaptic in periphery on non-neuronal cells |
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Term
| Alpha 1 receptors tend function as |
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Definition
| excitatory receptors by increasing Ca |
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Term
| Alpha 2 receptors are found |
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Definition
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Term
| alpha 2 receptors function as |
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Definition
| modulators/autoreceptors by inhibiting adenylate cyclase and as a result cAMP |
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Term
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Definition
1. arousal
2. focus/info gathering |
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Term
| Alpha or beta receptor mainly in the brain |
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Definition
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Term
| Beta receptors primarily regulate |
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Definition
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Term
| What binds beta receptors better NE or epi |
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Definition
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Term
| Beta receptors function to |
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Definition
| increase adenylate cyclase activity and thus cAMP |
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Term
| example of neuroactive peptide |
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Definition
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Term
| Where is neurotensin found |
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Definition
| prefrontal/limbic cortex, hypothalamus and midbrain |
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Term
| Neurotensin is always colocalized with |
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Definition
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Term
| Peptide neurotransmitters in general are |
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Definition
| colocalized with other NT and affect and are affected by these NT |
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Term
| Reason for co-localization |
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Definition
| more refined and complex signals |
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Term
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Definition
| 170 AA protein w/ one copy of neurotensin and one copy of neuromedin N which are processed into final forms |
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Term
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Definition
| dense core vesicles ie granules which are larger than synaptic vesicles |
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Term
| How do neurotensin filled dense core vesicles get to axonal terminals |
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Definition
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Term
| Release of dense core vesicles is dependent on |
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Definition
| Calcium but needs high intensity rapid firing b/c needs much more calcium than synaptic vesicles but remember dopamine would be released early b/c normal synaptic vesicles so neurotensin released in extreme cases |
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Term
| Where can dense core vesicles be released from? |
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Definition
| anywhere not just at the active zone so less targeted |
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Term
| Are dense core vesicles refilled after release |
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Definition
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Term
| Inactivation of neurotensin |
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Definition
1.nonselective peptidases
2.diffusion
3.no reuptake by transporters but can be taken into cell with receptor for intracellular signaling |
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Term
| Peptide signaling generally |
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Definition
| lasts longer but less directed |
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Term
| Neurotensin receptors are |
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Definition
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Term
| Neurotensin receptors have |
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Definition
| very high affinity b/c protein is larger so can form more bonds |
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Term
| Consequences of increase neurotensin receptor affinity |
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Definition
| receptors can get activated at lower concentrations so can maybe compensate for decreased amount release, further travel and less direction |
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Term
| Activation of dopamine autoreceptors have what affect on neurotensin release |
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Definition
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Term
| example of neuroactive lipid |
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Definition
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Term
| Anandimide mimics the effects and binds to same receptor as |
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Definition
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Term
| Where is anandamide distributed |
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Definition
| throughout the brain but highest amounts in the striatum, limbic cortex, hippocampus and cerebellum |
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Term
| Anandamide functions (generally) |
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Definition
| to modulate many fundamental brain processes |
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Term
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Definition
1. feeding,sleep, bp, balance, posture, memory, mood
2.KEY one is modulates other neurotransmitters |
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Term
| Ananamide synthesis occurs |
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Definition
| on demand it is not stored |
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Term
| What is the precursor to anandamide |
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Definition
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Term
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Definition
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Term
| What is regulatory enzyme of Anandamide synth |
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Definition
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Term
| Transacylase is turned on by |
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Definition
| increased calcium means increased neuronal activity |
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Term
| What is converted directly to Anandamide in the synthesis |
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Definition
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Term
| What converts NAPE to anandamide |
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Definition
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Term
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Definition
| no vesicular storage made on demand |
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Term
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Definition
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Term
| What inactivates anandamide |
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Definition
| FAAH-fatty acid amide hydrolase which cleaves anandamide into arachidonic acid and ethanolamine |
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Term
| What is the anandamide receptor |
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Definition
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Term
| CB1 is what type of receptor |
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Definition
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Term
| What kind of receptor does anandamide bind to ionotropic or metabotropic |
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Definition
| metabotropic-g protein coupled |
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Term
| Where is CB1 mostly located |
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Definition
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Term
| What is the action of CB1 activation by anandamide |
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Definition
| inhibits the opening of voltage regulated Ca channels presynaptically so it inhibits neurotransmitter release |
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Term
| Anandamide has what kind of activity |
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Definition
| activity dependent, retrograde inhibition of neurotransmitter release |
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Term
| Where does synthesis of anandamide occur when neuronal activity is high |
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Definition
| post synaptic cells (dendrites) because retrograde inhibitor of neurotransmitter release |
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Term
| In what situation do anandamide levels increase and why? |
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Definition
| Stroke seizures and brain trauma b/c thought to be a protective agent against excitotoxicity |
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Term
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Definition
| increased anandamide levels in the CSF |
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