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72 Cards in this Set
- Front
- Back
What are the two major components of the BBB?
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tight junctions
glial endfeet |
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What 4 molecules (or types of) may pass the BBB via passive diffusion?
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H2O
CO2 O2 FREE steriod hormones |
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How does glucose cross the BBB?
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GLUT-1 transporters on capillaries (and astrocytes)
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Which direction do Na, K, & Cl move via their collective transporter?
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from CSF to blood
expression of this transporter is tied to endothelin 1 and 3 |
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If many drugs can readily cross the BBB, what stops them?
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P-glycoprotein moves them back to the blood
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These areas are neural tissue that is "outside" or not quite as protected by the BBB as other neural tissue.
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What are the circumventricular organs?
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What are the 4 "exceptions" to the BBB?
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1. Post pituitary
2. area postrema: vomiting 3/4> OVLT (organum vasculosum of lamina terminals) & subfornical organ: control body water/thirst/BV |
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What three molecules are found in relatively equal concentrations in the plasma and CSF?
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Na
Cl HCO3 |
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What three molecules are found in GREATER concentration in the CSF compared to plasma?
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Mg
CO2 creatinine |
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What four molecules are found in LESSER concentration in the CSF compared to plasma?
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K
Ca++ protein inorganic PO4 |
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What are the 3 central locations of Ach in the brain?
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cortex
thalamus striatum |
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How is Ach transported into viscles?
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via VAchT
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How is Ach catabolized?
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via acetylchoniesterase
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What muscarinic receptor type is found in the CNS?
What is the effect? |
M1: inc IP3/DAG --> Inc Ca++
serpentine, g-prot receptor |
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What are the characterstics/locations of nicotinic receptors?
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1. ionotropic --> allow Na+ entrance
2. NMJ, autonomic ganglia, other parts of CNS |
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What are the 5 monoamines?
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E
NE dopamine serotonin histamine |
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Where can you find E & NE in the CNS?
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E: medulla
NE: locus ceruleus, other pontine/medullary areas |
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How does E/NE get into transport vesicles?
What inhibits uptake? |
VMAT1
VMAT2 Reserpine inhibits |
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What two enzymes can degrade E/NE?
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monamine oxdase
COMT (in glial cells/post-syn membrane) |
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What is the molecular effect of binding to beta-ad receptors?
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all inc. cAMP
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What is the effect of binding to the following alpha-ad receptor types?
1. 1a, b, and d 2. 2a, b, and c |
1. inc IP3/DAG --> dec gK+
2. dec cAMP --> dec Ca++ & inc. K+ |
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What 4 areas of the brain can you find dopamine?
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basal ganglia
hypothalamus limbic system cortex |
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What kind of receptors bind dopamine? What are the subtype groupings based on effect?
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1. serpentine receptors --> G proteins
2. D1/D5 --> inc cAMP D2: dec cAMP --> dec gCa and Inc. gK+ D3/D4: dec cAMP |
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Where can you find serotonin in the CNS (5 places)?
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hypothalamus
limbic system cerebellum brainstem raphe nuclei spinal cord |
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What serotonin receptor subtype is ionotropic?
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5HT3 --> Na+
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What serotonin receptor subtype is a target for selective anti-depressants?
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5HT6
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What serotonin receptor subtype is found in the limbic system?
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5HT7
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Where can you find histamine in the CNS?
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hypothalamus (wakey wakey)
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How is histamine catabolized?
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DIAMINE oxidase and COMT
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Which histamine receptor subtype is found in the presynaptic membrane.... and decreases its release?
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H3
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Which histamine receptor subtype is involved in wakefulness?
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H1
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What are the 5 important NT's in the amino acid class?
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excitatory: glutamate, aspartate, taurine
Inhibitory: GABA, glycine |
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What 3 places can you find GABA?
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cerebellum
cortex retina |
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What enzyme makes GABA?
What is its precursor? |
1. GAD (glutamate decarboxylase)
2. derived from glutamate |
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What are the characteristics of GABA-A receptors?
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ionotropic
5 subunits inc. Cl- conductance benzodiazepine potentiates! |
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What are the characteristics of GABA-B receptors?
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serpentine
herterodimer G protein effects :dec andylyl cyclase inc IP3/DAG inc. gK+ |
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What is the major inhibitory NT of the brian?
Spinal cord? |
brain: GABA
spinal cord: glycine |
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Where can you find glycine in the CNS?
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SPINAL CORD
brainstem forebrain |
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What are the characteristics of glycine receptors?
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ionotropic
pentamer alpha sub binds the NT Cl- channel strychnine BLOCKS! |
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What NT class do opiods belong to?
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peptides
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In what 4 parts of the CNS can you find opiods?
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basal ganglia
hypothalamus parabrachial nuclei raphe nuclei |
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What are 4 key precursor molecules of opiods?
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proenkaphalin
pro-opiomelanocortinin (for endorphins) prodynorphin endomorphin |
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What enzymes can degrade opiods?
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enkephalinase A/B
aminopeptidase |
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What are 3 important effects of opiods binding to their serpentine u (mu) receptors?
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analgesia
respiratory depression euphoria |
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What are 2 important effects of opiods binding to their serpentine kappa receptors?
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analgesia, dysphoria
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What is the main effect of opiod-binding to delta receptors?
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analgesia
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What are two vital components to brain functioning (molecules)?
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calcium
oxygen |
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What EAA is found in the visual cortex & pyramidal cells?
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aspartate (from OAA)
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What is the ionotropic receptor of EAA's?
What is the effect of receptor binding? |
NMDA receptors --> allow Ca++ influx (and a little Na+)
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What other molecule must be present in order for EAA to have its effect on NMDA receptors?
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glycine (it is a co-agonist)
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What ion sits in the NMDA receptor channel, blocking Ca++ influx?
What must happen to remove it and open the channel? |
1. Mg++
2. membrane depolarization causes it to leave |
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What drug can bind the NMDA receptor internally and block it?
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PCP
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Activation (and Ca++ influx) of NMDA receptors leads to what overall outcome?
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EPSP (slow onset but prolonged duration)
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Activation of non-NMDA receptors causes influx of what?
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Na+ ( and a little Ca++)
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What are the two (pharmacological) subtypes of non-NMDA receptors?
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AMPA
kainate |
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What drug can bind to AMPA receptors and inhibit response to EAA's?
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benzodiazepine
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What important relationship accounts for interplay b/w AMPA/kainate receptors w/ NMDA receptors?
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they are often co-localized soo.......
activate non-NMDA --> Na+ influx --> membrane depol --> Mg++ release from NMDA --> Ca ++ influx can now occur |
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Are EAA metabotropic receptors located pre or post-synaptically?
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trick! both locations
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This type of EAA receptor is found in primary afferent neurons and premotor (upper mn) neurons.
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What are non-NMDA receptors
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These EAA receptors are associated with long-term changes in synaptic strength, learning, and memory.
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What are NMDA receptors
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These EAA receptors are associated with learning, memory, and motor systems.
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What are metabotropic receptors?
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How can glia catabolize EAA's?
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convert it to glutamine and relase it into the ECF --> neurons can convert back to glutamate
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How is EAA function connected with NO?
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influx of Ca++ --> bind calcineurin --> activate NOS -->arginine converts to NO --> long-term potentiation and memory (and CV/resp. control)
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Why can NO be very toxic?
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leads to production of free radicals
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What are 5 pathological/clinical situations in which excitotoxicity is implicated?
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cerebral ischemia/stroke
hypoxia/anoxia trauma to CNS hypoglycemia possibly epilepsy |
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What happens to the cell membrane when cells can't meet metabolic demands?
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depolarization
(trigger for EAA release?) --> NMDA activation --> Ca++ influx in cells --> baaaad |
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increased intracellular Ca++ leads to activation of what 4 intracelllular paths?
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activates:
PLA2 calcineurin u-calpain (a protease) apoptosis |
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Activation of PLA2 via Ca++ causes release of what in the cell?
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arachidonate (physical damage to the membrane)
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What is the effect of calcineurin in the cell?
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increases NO synthesis
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mitochondrial membrane disruption leads to activation of what 2 apoptotic molecules?
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cytochrome C
caspase 9 .... this activates caspase 3 --> proteolysis/apoptosis |
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Why is introducing oxygen to a ischemic (damaged) cell problematic?
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oxygen often ends up as free radicals
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In reperfusion injury, kinsases convert ATP to what?
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ADP + PO4 --> phosphorylation and further mod of proteins
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