Receptors and signalling

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123 Terms

1
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how do drugs exert their action
by binding to proteins
2
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4 classes of proteins targeted by drugs
ion channels, enzymes, ion channels receptors
3
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what are ion channels
protein channels in the membrane that allow lipophobic /hydrophilic molecules through
4
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which ion channels to drugs target
involved in neurotransmission
5
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examples of drugs that target neurotransmission
sodium channel blockers

gabapentin
6
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how does gabapentin work
targets voltage gated calcium ion channels to prevent its movement and prevent AP
7
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role of receptor targeting
regulates cellular processes

enables communication between cells

enables coordination of tissue, organ and bodily responses
8
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how do drugs causes side effects despite being targeted
off target effects can occur which occurs from interactions with receptors in multiple organs
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what is an example of a drug and its side effects
opium has analgesic and euphoric effects but can cause constipation and respiratory diseases
10
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how does opium use lead to addiction
activation of reward pathways and changes in receptor function (tolerance)
11
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what is the cause of death in opium addicts
respiratory disease and suffer from chronic constipation
12
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how do receptors help in drug function
allows for specificity in drug function
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which type of receptor does not pass through the membrane
steroid
14
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what do ionotropic, metabotropic and kinase linked receptors have in common
they are found on the cell surface and have transmembrane spanning segments of 20-25 hydrophobic amino acids
15
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what is a feature and function of DNA linked receptors
regulates gene transcription

ligand must be able to cross the plasma membrane (lipophillic)
16
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what is an example of a DNA linked receptor
oestrogen receptors
17
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what is a ligand
any molecule that binds to the receptor
18
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what is a Agonist
drugs or chemical mediators that bind to a receptor producing a response
19
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examples of agonists
pilocarpine, nicotine, aCh, morphine
20
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what is an antagonist
does not a cause a downstream response or prevents/ inhibits the response of an agonist e
21
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examples of antagonists
atropine curare
22
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how long is the signal transduction of ionotropic, metabotropic, kinase-linked and nuclear receptors
mms, s, hrs, hrs
23
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what is an example of a LGIC
nicotinic ACh receptor
24
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what is an example of a metabotropic receptor
Muscarinic ACh receptor
25
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what is an example of a kinase-linked receptor
cytokine receptor
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what is an endogenous receptor
a compound naturally produced by the body which binds and activates the receptor
27
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what is the endogenous molecule for ionotropic receptors
small molecule chemical mediators not proteins
28
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what happens when a molecule binds to an ionotropic receptor
central aqueous pore opens
29
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how many transmembrane domains in GPCRS
7
30
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what structure do GPCRs have
alpha helical structure
31
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what is a heterotrimeric GTP binding protein
g protein
32
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when do lignad gated ion channels open
when they are bound by an agonist
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what does activation of an ionotropic receptor by excitatory neurotransmitters cause
membrane depolarisation and action potential firing
34
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where are nicotinic acetylcholine receptors found?
neuromuscular junction, autonomic ganglion neuron, brain neurones
35
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what is the agonist for NaChR
ACh and nicotine
36
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what is the antagonist for NaChR
tubocurarine (curare)
37
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examples of ionotropic glutamate receptors
AMPA and NMDA
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what are the 2 most common receptors
ligand gates and G protein coupled
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what are most hormones detected by
GPCRs
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what is the structure of GPCRs
a single protein and spans the membrane 7 times
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how do GPCRs work?
regulate effector proteins via heterotrimeric GTP binding protein
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what is the structure of a g protein
1 alpha, 1 beta, 1 gamma (heterotrimeric)
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how does signal transduction occur in GPCRs
via activation of g proteins
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how are g proteins selective
they can be made up of 30 different alpha, beta and gamma units to make different g proteins which interact with different GPCRs and effectors
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how many members of the GPCR family are there
800+
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what do GPCRs respond to
hormones, inflammatory mediators and chemokines
47
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why does GPCR signal transduction take longer than LGIC?
it is cascading and involves changing the function of different proteins
48
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where is the ligand binding site in an opioid receptor
buried within the transmembrane receptors
49
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what happens when the ligand is bound to a GPCR
it will make contact with several amino acids which influences the structure that the receptor will adapt
50
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which effectors can g proteins control
ion channels, enzymes
51
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types of ligand gated ion channels
cys-loop

ionotropic glutamate

P2x

calcium release
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examples of cyc-loop type receptor & assembly
nAChR, GABAa 5HT3

pentameric
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exmales of ionotropic glutamate type receptor and assembly
NMDA

tetrameric
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example of P2X type receptor and assembly
P2XR

trimeric
55
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examples of calcium release type receptor and assembly
IP3R, RyR

tetrameric
56
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what are LGIC used for
fast synaptic transmission
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what are the endogenous agonsists for LGIC
fast classical neurotransmitters stored in vesicles
58
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what are LGIC composed of
3-5 subunits
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how many transmembrane domains does each LGIC subunit have
2-5
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when does a LGIC close
when the agonist is removed or the receptor enters a desensitised state
61
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what causes changes in the excitability of a cell
ions flowing through open LGIC
62
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what happens in the activation of ionotropic receptors for inhibitory neurotransmitters
membrane depolarisation is inhibited

action potential firing is reduced
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what is an example of a receptor for an inhibitory neurotransmitter
GABAaRs expressed by the brain w
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what is the agonist for GABAaRs
GABA, phenobarbitone
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what is the antagonist for GABAaRs
Picrotoxin
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what is phenobarbitone used for
epilepsy
67
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what is the use of picrotoxin
CNS and respiratory system stimulant
68
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what is myasthenia gravis
an autoimmune disease where the body creates antibodies to skeletal nicotinic acetylcholine receptors
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what are the symptoms of myasthenia gravis
increasing muscle weakness, eye drooping
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how many people suffer with myasthenia gravis
1 in 2000
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how is myasthenia gravis treated
anti-cholinesterase to prevent the breakdown of ACh, and immunosuppressants
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example of an anticholinesterase
neostigmine, pyridostigmine
73
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why are some GPCRs referred to as orphans
because the ligand they respond to has not been identified
74
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when does signal transduction occur
following an agonist binding to a GPCR and activation of a g protein
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one G protein is used by _______ receptor
more than one
76
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how do g proteins achieve signal transduction
by undergoing an enzymatic cycle
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which g protein subunits interact with effectors
alpha and beta
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what happens when the agonist is bound to the GPCR
it stabilises the helices and activates signalling
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what happens when the antagonist is bound to the GPCR
it interacts differently with amino acids and adopts a shape not conducive to signalling
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what happens after agonist binding to GPCRs
signal transduction via g proteins which control the function of effectors
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how many types of g proteins are there
20
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what are second messengers
small diffusible molecules that spread signals
83
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how do noradrenaline and adrenaline work
via g protein coupled receptors
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where is the binding site of the g protein
the alpha subunit
85
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what is the role of GDP
associated with the inactive GPCR
86
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how is GDP suited to bind to an inactive GPCR
has a very high affinity to beta-gamma subunits in GPCRs
87
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how is the g protein activated after agonist binding
agonist becomes very attracted to the alpha subunit and associates with it

causes a change in the structure of alpha lowering GDP affinity for GTP instead

GTP replaces GDP and g protein is activated
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what do g proteins need to be activated
GTP
89
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what part if the g protien is a GTPase
alpha
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what is a GTPase
binds and hydrolyses GTP
91
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what is the limiting factor in GPCR signalling
receptor number
92
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how is the g protein inactivated
GTPase activity is activated in alpha and GTP loses a phosphate to become GDP

conformational changes increase attraction to beta-gamma subunit and reforms heterotrimeric g protein

alpha\` subunit no longer attracted to effector molecule and beta gamma no longer regulating protein
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Gs protein
stimulates adenyl cyclase to make cAMP
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Gi protein
inhibits adenyl cyclase leading to a cAMP decrease
95
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Gq
increases phospholipase C

increased IP3 and DAG

increases calcium intake
96
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what is phospholipase c
an enzyme effector modulated by g protein
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which subunits regulates the activity of enzymes
alpha
98
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what causes an increase in pKA activity
increased cAMP
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what is cAMP
a second messenger that can diffuse into the nuclease to regulate proteins
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what is cAMP broken down by and into
phosphodiesterase into 5AMP