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Definitions |
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catecholamine precursor
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tyrosine
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glycine precurors
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serine
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serotonin precursor
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tryptophan
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Norepinephrine--ß receptor--*Agonist*
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Isoproterenol
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Norepinephrine--α receptor--*Antagonist*
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Phenoxybenzamine
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ATP post-synaptic effect
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excitatory
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Histamine
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Monoamine
decreases = depression
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catecholamine post-synaptic effect
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excitatory
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Dopamine
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Influences movement, learning, attention, and emotion
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Dopamine synthesis
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tyrosin->Dopa (tyrosine hydroxylase)->dopamine (AADC)tyrosine hydroxylase is rate-limiting and its activity is saturated at normal levels so adding more tyrosine wont contribute to more catecholamine synthesis (transporter for Phe and Tyr across BBB also saturated)
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histamine vesicles
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large dense-core vesicles
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ATP properties
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excitatory post-synaptic effectprecursor is ADPrate-limiting steps are glycolysis and mitochondrial ox-phosremoval is by hydrolysis to adenosine and AMPvesicles are small clear-core vesicles
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catecholamine removal
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transporters; MAO; COMT
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VMAT
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vesicular monoamine transporter
loads dopamine into synaptic vesicles at the nerve terminal
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neuropeptides vesicles
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large dense-core vesicles
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ASSOC WITH DRUG REWARD
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DA
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Malfunction of GABA
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Seizures, tremors, insomnia
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Ach storage vesicle
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small clear-core vesicle
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Types of Amino-Acid Neurotransmitters.
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GABAGlutamic AcidGlycine
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MAO
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dopamine catabolism enzyme contained in both neurons and glia
monoamine oxidase
inhibited by antidepressants
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neuropeptides post-synaptic effect
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excitatory and inhibitory
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ACh Receptor Subtypes
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Nicotinic and Muscarinic
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Serotonin
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CNS, affects sleep, mood, attention and learning, inhibits
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what are antagonists of muscarinic receptors?
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atropine
scolopolamine
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COMT
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present in nervous system and peripheral tissues; extracellulary in synaptic cleft, degrades NT after releasebroad catechol substrate specificitymethylates one of the hydroxyl groupsinhibitors: entacapone, tolcapone
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Gamma-aminobutyric acid
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inhibitor, decreases in appetite, disruptions in sleep
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Norepinephrine
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helps control mood and arousal undersupply can depress mood (fear/anexiety) also linked to basic motivation like hunger and thirt
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what are the adregernic receptors?
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alpha 1-everything
alpha 2-presynaptic inhibition
Beta 1-heart
beta 2-lungs
beta 3-adipocytes
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Ach synthesis rate-limiting step
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CAT (choline acetyl transferase)
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Peptide hormone
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Comes off ribosome as a preprohormone
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Norepinephrine Receptor Subtypes
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α receptor and ß receptor
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what is the most common inhibitory NT in CNS?
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GABA
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glutamate toxicity
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elevated levels of Glu are neurotoxic and is released in excessive amounts by neurons in pathological conditionsit can activate many synapses and cause huge Ca++ release which kills neurons
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ALSO, CATECHOLAMINES AND GLUTAMATE
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2 TYPES OF ACH RECEPTORS
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synthesis of norepinephrine
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synthesized in vesicle from dopamine by dopamine-B-hydroxylase, which is bound to the inner surface of the vesicle
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tyrosine hydroxylase
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converts tyrosine to DOPA in first and rate-limiting step of catecholamine synthesis
requires oxygen and tetrahydrobiopterin as co-factors
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functions of plasma membrane reuptake
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1. terminate action at receptor2. prevent diffusion to other synapses3. recycle supply4. can run in reverse if NT levels are high intracellularly
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what are the 2 types of neurotransmitters and how do they differ?distinguish between how they are released and what type of synaptic actions they mediate
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small molecule neurotransmitters (subset of this group is the biogenic amines) and peptide neurotransmitterssmall molecule transmitters are released by low frequency activity and mediate rapid synaptic actionspeptide transmitters are releasted by high frequency activity and mediate slower, ongoing synaptic actions
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From the adrenal gland you have the release of atleast four different hormones. Adrenal cortex synthesizes and releases 3 types of steroids:
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1. Glucocorticoids: cortisol 2 Mineralocorticoids: aldosterone 3. Androgens (andro=man)
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what does nerve gas do?
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irreversibly binds to ACh vesicles to prolong transmission
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name 4 components of neurotransmitter removal from synaptic cleft
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1. diffusion away from post-synaptic receptors2. re-uptake into pre-synaptic nerve terminal by transporter proteins3. uptake into nearby glial cells4. degradation by specific enzymes
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how does calcium enter the pre-synaptic neuron and what does it do?
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action potential depolarizes the cell, allowing voltage-gated calcium channels to open
calcium enters through open channels and stimulates fusion of synaptic vesicles with the pre-synaptic plasma membrane for neurotransmitter release
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Describe the transmission of neurotransmitters.
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When the synaptic cleft is too large to be jumped, the gap can be crossed using neurotransmitters located in sacs within the axon terminal (the end of the axon). The sac with the appropriate neurotransmitters is forced through the membrane into the cleft, releasing the neurotransmitters into the cleft. Neurotransmitters then make their way to receptor sites on the post-synaptic neuron, where they stimulate the neuron and the action potential begins again.
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what does the botulin toxin do?
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allows fewer vesicels of ACh to be released
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what is a co-transmitter and what is its significance?
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neurons often store and release 2 or more neurotransmitters (co-transmitters)a neuron can be excited by 1 type of neurotransmitter and inhibited by another type
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GABA precurors
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glutamine
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GABA precurors
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glutamine
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glutamate precursors
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glutamine
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GABA--GABAa receptor--*Antagonist*
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Bicuculline
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Glutamate--NMDA receptor--*Agonist*
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NMDA
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neuropeptides precursors
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amino acids
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glutamate post-synaptic effect
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excitatory
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Malfunction of Acetycholine
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Alzheimer's disease
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Ach properties
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excitatory post-synaptic effectrate-limiting step is CAT (choline acetyl transferase)precursors are choline + acetyl CoAremoval is by acetylcholinesterasestorage vesicles are small clear-core vesicles
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ATP vesicles
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small clear-core vesicles
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glycine synthesis rate-limiting step
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phosphoserine
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Ach properties
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excitatory post-synaptic effect
rate-limiting step is CAT (choline acetyl transferase)
precursors are choline + acetyl CoA
removal is by acetylcholinesterase
storage vesicles are small clear-core vesicles
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catecholamine properties
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excitatory post-synaptic effect
precursor is tyrosine
rate-limiting step in synthesis is tyrosine hydroxylase
removal is by transporters, MAO, and COMT
vesicles are small clear-core vesicles and large irregular dense-core vesicles
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HIGH SEROTONIN
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SZ AND AUTISM
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atropine
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pupil dilationblocker of muscarinic Ach receptor
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serotonin properties
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post-synaptic effect is excitatoryprecursor is trp and rate-limiting step in synthesis is trp hydroxylaseremoval is by transporters and MAOvesicles are large dense-core vesicles
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Schizophrenia
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Biochemical hypothesis that schiz symptoms such as hallucinations may be casued by an excess of dopamine.
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phenylethanol-amine-N-methyl transferase
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converts norepi to epi
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Glutamate Receptor Subtypes
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AMPA and NMDA
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Malfunction of Dopamine
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Schizophrenia, tremors, Parkinson's disease
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MAO inhibitors
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nonspecific irreversible inhibitors - increase presynaptic concentration of NTs and prolongs availability of released NTs
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ATP removal
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hydrolysis to AMP and adenosine
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what do catecholemines have in common as a precursor?
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L-tyrosine
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give 4 examples of small molecule neurotransmitters
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AchGABAglycineglutamate
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ATP synthesis rate-limiting step
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mitochondrial ox-phos and glycolysis
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Endorphins
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act within the pain pathways and emotion centers of the brain..lack of endorophins could lower pain threshold or reduce ability to self-soothe
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what agent causes NT to be released and depleted in the future?
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amphetamines
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metabolism of glutamate
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1. ionotropic (AMPA, NMDA, Kainate) and metabotropic receptors2. primary mechanism for inactivation is reuptake by pm Glu transporter3. astrocytes play a big role in inactivation and recycling - convert Glu to Gln via glutamine synthesis and transport it out of cell where neurons take it up via a glutamine transporter and convert it to Glu
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what are agonists of muscarinic receptors?
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ACh, muscarine, pilocarpine, oxotremorine
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overview of steps in synaptic transmission
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1. neurotransmitter synthesis2. storage in vesicles3. Ca entry4. neurotransmitter release5. binding to receptors6. degradation in cleft, metabolism, or diffusion from synapse7. reuptake8. recycling of vesicles9. neuromodulation by presynaptic receptors
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name the 5 biogenic amines
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the catecholamines: dopamine; epi; norepi
serotonin
histamine
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reuptake of Glutamate
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1. pm Glu transporter is primarily on astrocytes2. 5 subtypes differing in affinity, specificity, and location3. highly effective at lowering extracellular Glu concentration - acts as buffer
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describe the cycle of transmission between electrical synapses
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action potential generates electrical current, which flows directly from one neuron to another through pore in that comprises gap junctiontransmission is bidirectional and very fast
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how does cocaine work?
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it binds to DAT (dopamine transporter that transports dopamine out of synaptic cleft), increasing the dopamine concentration so dopamine is more available to receptors
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synthesis of small molecule neurotransmitters
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1. NT synthesis is regulated by neuronal activity levels2. synthesis occurs in the cytosol3. NTs are packaged in vesicles 4. cofactors include folic acid, SAM, O2, Cu, vitamins C, B6, B12
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describe the structure and function of a nicotinic Ach receptor
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activated by both nicotine and Achsame molecule is both receptor and cation channel (ionotropic receptor / ligand-gated ion channel)large protein complex with 5 subunits around a central membrane-spanning poreeach subunit has 4 transmembrane domains that comprise the ion channel pore and a long extracellular region where the Ach bindsintimate association of Ach with channel pore allows rapid (ionic) response to Achresults in excitatory post-synaptic responses
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where is dopamine found?
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in the CNS and PNS in vesicles of cells which release NE and EPI
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What are the Blocking Agents of Ach (nicotinic)?
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1) d-turbo curarine2) succinyl choline->blocks muscle activity
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name the 2 precursors and the enzyme used to synthesize Ach
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Acetyl CoA (from glucose metabolism) and cholineenzyme is CAT = choline acetyltransferase
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