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79 Cards in this Set
- Front
- Back
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Autocrine
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Chemical messaging where a cell releases a chemical that binds to itself
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Intracrine
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Chemical messaging inside the cell
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Paracrine
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Chemical messaging between neighbouring cells
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Neuroendocrine
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Products from neurons released into the blood
Cell recieves and propagats action potentials as usual but at the axon terminal, product is released |
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Neurotransmitters in blood
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Per definition, neurotransmitters in blood are called hormones instead
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Chemical synapse
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Connection between two neurons where the pre-synaptic neuron releases neurotransmitter recieved by the post-synaptic neuron. (Most common)
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Gap-junction
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Also 'electrical synapse'
Aligned connexons on the membrane allow ions or second messengers to flow through, thus conducting electrical signal. Very fast signal transduction between neurons. |
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Neuron communication
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Chemical synapse and gap-junction
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Connexon
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Membrane protein in gap-junction
Aligned between pre- and post-synaptic Allows ions to flow through, thus allowing neuron communication. Also allows messenger molecules Made of 6 connexins |
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Innexins
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Non-vertebrate version of connexon; comparable function but not the same origin
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Glial cells
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Support neurons metabolically
Coupled to neurons through gap-junctions |
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Messenger molecules
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neurotransmitters and hormones
(hormones when released in blood; some chemicals may take either function in different context) |
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hydrophilic / hydrophobic
importance? |
Water / fat soluble
1. hydrophilic cannot cross cell membrane, so bound to receptor on outside, transmembrane signal transduction initiates a change inside 2. hydrophilic cannot reach/leave brain cells because of blood brain barrier |
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solubility of:
proteins peptides amino acids |
all water-soluble
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neurotransmitter structures
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peptides
(modified) amino acids Generally hydrofilic |
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hormones structures
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proteins
peptides (modified) amino acids Some are hydrophobic |
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steroid hormones
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Derived from cholesterol
Hydrophobic; used to signal across BBB |
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thyroxin
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Derived from two tyrosine molecules
Hydrophobic |
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tight-junctions
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parallel protein structures between blood cells in the brain that make it impenetrable for hydrophilic substances
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CSF
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cerebrospinal fluid
liquid found in the ventricles (hollow fluid filled cavities) and in the extracellular space of the brain |
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BBB
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Blood brain barrier
Blood vessels in the CNS don't allow hydrophilic substances in or out, creating a barrier to those substances and preserving a very low protein concentration in the CSF Very effective, especially against larger molecules |
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heroine / morphine
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Heroine is alike to morphine but it is hydrophobic (so can pass the BBB) and does not bind to receptors. However, it can be converted to morphine easily, making it much more effective in the brain
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Oestrogen and the BBB
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Oestrogen, as a steroid hormone, can cross the BBB, having effects in- and outside CNS (sexual behaviour and preperation for pregnancy)
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Peptides and the BBB
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Peptides can generally not bross the BBB. Hence one type of peptide can have different functions in- and outside
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CCK two functions
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CNS: neurotransmitter
Periphery: gut hormone that indicates food in gut (No interference due to BBB) |
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Getting across BBB
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BBBD
Lipidization Transporters |
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BBBD
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BBB disruption; inject high osmotic pressure of glucose, disrupting tight junctions for 20-30 minutes
Gets things across BBB, but leaves brain valuable to infections or damage from even normal proteins |
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Lipidization
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Attach hydrophobic group to get across BBB. Without getting too big or losing effectivity of drug
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Transport systems
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System to transport specific molecules across the BBB (e.g. transferin)
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Transferrin
+ use |
Iron (Fe) binding protein, to transport Iron across BBB
aBind drug to antibody for transferrin; utomatically transported over BBB |
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antisense mRNA
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hybridizes with the mRNA forming a double stranded RNA that can not be translated
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Peptides
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Short (<~50) polymers of amino acid monomers linked by peptide bonds
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Neuropeptide synthesis
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Synthesized from large precursor proteins (pro-hormones) made in neural cell body.
Neuropeptide is always inside a comparentment of lipid membranes: RER, Golgi, secretory granules. Activation enzyme is always with it but is only activated in acidic conditions in secretory granules. |
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Exocytosis
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Granules containing transmitter fuse with membrane, signalling other cells
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Small molecule neurotransmitter systhesis
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Amino acids in axom ending are modified by enzymes made in ribosomes, which are transported by natural cytoplasm flow. Amino acids are created and pumped into vescicles
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After neurotransmitter release
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Options:
1) Bind postsynaptic receptor 2) Broken down by enzymes 3) Reabsorbed by high affinity pumps (pre-synapse) |
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transmembrane transport of neuropeptides
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Neuropeptides hydrophilic
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Proteins, peptides and enzymes membrane crossing
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Crossing happens by membrane fusion (on several occasions), so the hydrophilic substances never go through a membrane
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How does precursor protein (prohormone) gets into the lumen of the RER
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pushed through the membrane into the lumen during its biosynthesis
these proteins start with a signal sequence (~25 amino acids), which indicates it should be synthesysed on the RER |
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Translation direction
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mRNA is translated from the 5’ to the 3’ end
N-terminalof the protein synthesised first |
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SRP
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signal recognition particle
when encountering signal sequence, blocks translation until transported to the RER docking protein |
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translocon
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Transports protein being synthesised over the membrane (of RER)
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glycoproteins
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proteins containing carbohydrate side chains
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Extracellular proteins vs neuropeptides
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Both synthesis in RER -> transfer vesicles -> Golgi -> plasma membrane
But neuropeptides are only released upon recieving a signal: "regulated pathway" |
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constitutive pathway
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Both synthesis in RER -> transfer vesicles -> Golgi -> plasma membrane; present in every cell to deliver extracellular proteins
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sortases
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Hypothetical proteins that make sure proteins for outside the cell are delivered to either the regulated or constitutive pathway
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endopeptidases
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Enzymes for (controlled) cutting of protein at specific sites
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trypsin
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An endopeptidases which cleaves at basic (protoc accepting) sequences
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PC
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Precursor convertases
Enzyme for cleaving precursor proteins. |
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PAM
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During protein cleavage, this enzyme additionally consumes glycine if present, and amidates the Cterminal of the protein
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amidation
+when, why |
Adding of amide to C-terminal of protein.
Happens mostly when glycine is last amino acid; this which provides the amide group on C-terminal Amidation is essential for some neuropeptides and hormones, and slows the breakdown of others. |
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acetylation
+why |
acetyl group on N-terminal
Acetylation can effect both the biological activity and the biological half-life of the peptides involved |
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POMC
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Proopimelanocortin; typical example of precursor protein with various cleavage sites and amidation site; leads to multiple proteins
* beta-endorphin - acts on opiate receptors * alpha-MSH - alpha-melanocyte stimulating hormone * ACTH - adrenocorticotropic hormone Different cleavage happens in different cells depending on the enzymes present (and of course fitting the purpose of those cells) |
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SMNT
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Small molecule neurotransmitters, or classical neurotransmitters
(distinct from neuropeptides) |
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Acetylcholine synthesis
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In cytoplasm
Through acetylation of choline By enzyme choline acetyl transferase (CAT). Acetyl donor: acetyl-CoA Actively transported into secretory vesicles |
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acetyl-CoA
(+synthesis location) |
Acetyl donor for acetylcholine synthesis
Prepared in mitochondria |
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Ach
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Acetylcholine
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Acetylcholine - once released
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Does not have a reuptake mechanism (unique among SMNT), but is broken down
Choline reupate presynaptically, used again for synthesis |
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Acetylcholine esterase
(function, location) |
Breaks down acetylcholine
Convert heroin to morphine Bound to postsynaptic membrane |
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GPI anchors
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common way of anchoring proteins to membranes
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Nicotine
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Can cross BBB
Reward center: addiction Cortex: attention, increased alertness |
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Acetylcholine - applications
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Wide distribution (in and outside CNS)
Especially in cholinergic neurons of the basal forebrain; inducing alertness or attention |
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Attention experiment
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Animal repeatedly has to choose the correct one of two levers based on a pattern of lights to get a reward; better performance is better attention
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Catecholamines - general
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Group containing dopamine, adrenaline and noradrenaline (structurally and functionally comparable)
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Catecholamines - synthesis
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From tyrosine in a chain of enzymatic reactions
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Tyrosine hydroxylase, TH
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Rate limiting enzyme in catecholamines synthesis
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Catecholamines - receptors
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G protein coupled receptors
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SMNT - immunocytochemistry
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Difficult to produce an antisera
Usually antisera produced for the enzyme creating the SMNT If you need to distinguish different catecholamines, you need to target a (combintion of) enzyme(s) later in the chain, because the beginning is identical for dopamine, adrenaline and noradrenaline |
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Catecholamines - once released
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Can be broken down
But mostly reupate by |
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Cocaine
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Inhibits catecholamine reuptake (upregulation)
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DAT
+inversion? |
Dopamine transporter; pumps Na+ along with gradient and DA against gradient (so no netto energy required)
No Na+ inversion during action potential at nerve terminal, because Na+ channels replaced by Ca2+ |
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DA (meaning)
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Dopamine
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VOCC / VONC
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Voltage operated Ca2+ / Na+ channel
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Amphetamines
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Can reverse the DAT dopamine transport (mechanism unknown)
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Serotonin
(effect, synthesis) |
“calming” or “mood elevating” effect
Synthesized from the amino acid tryptophan |
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Serotonin
(disruption x2) |
Lack of tryptophan (from which serotonin is made) might lead to disrupted signalling and therefore mood disorders
Prozac blocks re-uptake, enhancing signalling (and as such elevating mood and decreasing hyperactivity) Blocking re-uptake may lead to serotonin being broken down, making situation worse long-term |
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Second messenger
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Class of molecules that transmit a signal from outside (on the membrane) to inside the cell (not an enzyme, just a messenger molecule)
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Name the 9 neurotransmitters discussed
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Acetylcholine
Dopamine Adrenaline Noradrenaline Serotonin Glutamic acid Gamma aminobutyric acid (GABA) Glycine Purines |
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BOLD
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Blood oxygen level - images, produced by MRI
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