Lieb Flashcards
(200 cards)
1
Q
energy consumption
A
20% of total energy
2
Q
BBB
A
maintains neurogenesis, energy utilization, amyloid beta clearance, learning and memory
HEALTHY: tight junctions, controlled transcellular transport, p-Gp pump A-b -> HOMEOSTATIC MILIEU
AGED: leaky tight junctions, impaired energy utilization, cognition and neurogenesis, A-b accumulation -> NEUROTOXIC & NEUROINFLAMMATORY MILIEU
3
Q
BBB
function
A
maintains neurogenesis, energy utilization, amyloid beta clearance, learning and memory
4
Q
BBB
young & healthy
A
tight junctions, controlled transcellular transport, p-Gp pump A-b
-> HOMEOSTATIC MILIEU
5
Q
BBB
aged
A
leaky tight unctions, impaired energy utilization, cognition and neurogenesis, A-b accumulation
-> NEUROTOXIC & NEUROINFLAMMATORY MILIEU
6
Q
all cell types in NS (all metioned ones)
A
GLIA: astrocytes, myelinating glia (oligodendro, Schwann), ependymal, microglia
NEURONS
7
Q
Glia cells
A
- Astrocytes: influence neuronal growth, control extracellular milieu (glu, K+), similar receptors as in neurons
- Myelinating glia: oligodendro & Schwann, myelin sheath for saltatoric transmission, oligodendrocytes for waste clearing and remodeling of neuronal connections
- Ependymal cells: line ventricles, important during development
- Microglia: waste clearing and remodelling of neuronal connections
8
Q
Astrocytes
A
Glia cells
- influence neuronal growth
- control extracellular milieu (glu, K+)
- similar receptors as in neurons
9
Q
Myelinating cells
A
Glia cells
- oligodendro & Schwann cells
- myelin sheath for saltatoric transmission
- oligodendrocytes for waste clearing and remodeling of neuronal connections
10
Q
Oligodendrocytes
A
Myelinating glia cell
- waste clearing
- remodelling of neuronal connections
11
Q
Ependymal cells
A
Glia cells
- line ventricles
- important during development
12
Q
Microglia
A
Glia cells
- waste clearing
- remodelling of neuronal connections
13
Q
cell types important for cranial waste clearing
A
- oligodendrocytes
- microglia
14
Q
cell types important for remodelling of neuronal connections
A
- oligodendrocytes
- microglia
15
Q
NEURONS
parts
A
- somata (organelles)
- membrane (isolator)
- cytoskeleton (microtubuls, microfilaments, neurofilaments)
- axon (output)
- dendrites (input)
16
Q
NEURONS
Types + Example
A
- unipolar (invertebrate neuron)
- bipolar (bipolar neuron retina)
- pseudo-unipolar (DRG neuron)
- multipolar (motor neuron, pyramidial cell, purkinje-cell)
17
Q
invertebrate neuron
neuron type
A
unipolar
18
Q
DRG neuron
neuron type
A
pseudo-unipolar
19
Q
motor neuron
neuron type
A
multipolar
20
Q
purkinje cell
neuron type
A
multipolar
cerebellar neuron
21
Q
pyramidial cell
neuron type
A
multipolar
hippocampal neuron
22
Q
NEURONS
Soma
A
high K+, low Na+
location of organells
- nucleus
- rER for membrane proteins
- free ribosomes for cytosolic proteins
- sER for protein folding, regulates internal Ca2+, post-translationl modifications
- mitochondria
23
Q
NEURONS
cytoskeleton
A
MICROTUBULES
- anterograde kinesin, retrograde dynein
- assembly via GTP-hydrolysis
- drug target (vinca alkaloids assembly, taxene disassembly)
MICROFILAMENTS: 2 actin strands -> fiber -> mesh
NEURONFILAMENTS: structural integrity of esp. large axons
24
Q
microtubules
A
- anterograde kinesin, retrograde dynein
- assembly via GTP-hydrolysis
- drug target (vinca alkaloids assembly, taxene disassembly)
25
microfilaments
2 actin strands -> fiber -> mesh
26
neurofilaments
structural integrity of esp. large axons
27
NEURON
axon
area of output
- axon hillock (initiation segment, no rER)
- axon proper (wire, myelin sheaths, can form axon collaterals)
- axon terminal (synapse, chemical or electrical)
28
locus of AP generation
Axon hillock = initiation segment
29
axon hillock
= initiation segment
locus of AP generation
30
axon proper
electrical wire
myelin sheaths
can branch into axon collaterals
31
axon terminal
= synapse, terminal button
chemical or electrical
32
NEURONS
dendrites
area of input
polyribosomes
33
polyribosomes
hallmark of dendrites
34
Nernst equation
calculates equilibrium potential across the membrane of one specific ion
35
equilibrium potentials (37°C)
calculated by Nernst equation
K: -80mV
Na: +62mV
Ca: +123mV
Cl: -65mV
36
ion concentrations (EC and IC)
K: 5nM EC, 100nM IC
Na: 150 EC, 15nM IC
Ca: 2nM EC, 0.0002nM IC
Cl: 150nM EC, 13nM IC
37
5nM EC, 100nM IC
K
38
150nM EC, 15nM IC
Na
39
2nM EC, 0.0002nM IC
Ca
40
150nM EC, 13nM IC
Cl
41
-80 mV equilibrium potential
K
42
+62 mV equilibrium potential
Na
43
+123 mV equilibrium potential
Ca
44
-65 mV equilibrium potential
Cl
45
equilibrium potential K
-80 mV
46
equilibrium potential Na
+62 mV
47
equilibrium potential Ca
+123 mV
48
equilibrium potential Cl
-65 mV
49
ion concentration (EC and IC) K
5nM EC, 100nM IC
50
ion concentration (EC and IC) Na
150nM EC, 15nM IC
51
ion concentration (EC and IC) Ca
2nM EC, 0.0002nM IC
52
ion concentration (EC and IC) Cl
150nM EC, 13nM IC
53
Goldman-Hodgkin-Katz equation
calculates the conductance of a neuron (membrane potential) at a specific time point (specific ion concentration)
in "normal" conditions usually -65 mV
54
calculates the conductance of a neuron (membrane potential) at a specific time point (specific ion concentration)
Goldman-Hodgkin-Katz equation
55
calculates equilibrium potential across the membrane of one specific ion
Nernst equation
56
measurment of ion flow
patch-clamp method
- cell attached
- whole cell
- outside-out
- inside-out
57
effect of outward stimulation
stimulus -> receptor potential (dependent on voltage of stimulus) -> AP (if threshhold potential is reached, frequency dependend on receptor potential)
58
parameters determing ion flow
electric driving gradient (ohms law)
ionic driving gradient
59
Na+/K+ ATPase
tetramer (2a2b)
OPENING:
- inward open when ATP bound
- 3 Na bind
- ATP hydrolysis -> closed
- ADP release -> open (outward)
- Na dissociates, 2 K bind
- inward open throuigh ATP binding
pathophysiology dependend on SU used, a1 omnipresent, a2 in muscle and brain, a3 in brain
60
Na+/K+ ATPase
opening process
tetramer (2a2b)
- inward open when ATP bound
- 3 Na bind
- ATP hydrolysis -> closed
- ADP release -> open (outward)
- Na dissociates, 2 K bind
- inward open throuigh ATP binding
61
Na+/K+ ATPase
structure
tetramer (2a2b)
62
diseases caused by Na+/K+ ATPase defect (examples)
FHM, RDP, AHC, CAPOS
63
FHM
familial hemiplegic migraine
can be caused by Na+/K+ ATPase defect
64
RDP
rapid-onset dystonia parkinsonism
can be caused by Na+/K+ ATPase defect
65
AHC
alternating hemiplegia of childhood
can be caused by Na+/K+ ATPase defect
66
CAPOS
Cerebellar ataxia
Areflexia
Pes cavus
Optic atrophy
Sensorineural hearing loss
can be caused by Na+/K+ ATPase defect
67
Ca2+ ATPase
3 main groups: SERCA, PMCA, SPCA
OPENING:
- 2 Ca bind inside
- Mg-ATP binding causes slight conformational change
- ATP-hydrolysis causes further change
- Ca dissociates inside, exchanged by 2 H+
- conformation with H+ unstable
- reverse to original state and Mg & H+ release
68
Ca2+ ATPase
opening process
- 2 Ca bind inside
- Mg-ATP binding causes slight conformational change
- ATP-hydrolysis causes further change
- Ca dissociates inside, exchanged by 2 H+
- conformation with H+ unstable
- reverse to original state and Mg & H+ release
69
Cl tranpsort
dependend on K gradient established by Na/K ATPase
KCC2 -> cotransport (efflux)
neonatal NKCC1 causes K efflux and Cl influx
70
NKCC1
neonatal Cl transporter
K efflux, Cl influx
re-expression in adults can cause epilepsy
71
KCC2
K-Cl cotransporter
K and Cl efflux
dependend on Na/K ATPase generated K gradient
72
receptor potential
definition
(small) fluctuations caused by ion flow (usually positive)
73
EPSP
ecitatory post-synaptic potential, addition of many (excitatory) receptor potentials
74
AP
action potential
generated if cell depolarizes above a certain threshhold, usually by temporal or spatial suzmmation of EPSPs
sometimes one EPSP is sufficient
75
IPSP
inhibitiory post-synaptic potential
inhibiting signal of e.g. interneurons
76
AP architecture and corresponding ion
rising phase -> Na
decay slope -> K
overshoot -> K
77
Voltage gated ion channels
essential for AP generation, defects cause so called channelopathies
usually rapid activation, fast inactivation via pore collapse and repeated ctivation leads to slow/inactivated state
78
VGSC
structure
voltage gated sodium channels
- kinda monomer (one alpha, one auxiliary beta)
- 4 TM domains with 6 TM regions each (24TM)
- VOLTAGE SENSOR S1-4 with S4 positively charged
- PORE FORMATION by S5-6
- MODULATION by linker between dom 1&2
- INACTIVATION by linker between dom 3&4
79
VGSC
opening
voltage gated sodium channels
- IC positive charge pushes S4 outwards
- pore opens
- linker between domain 3&4 collapses into the pore
80
VGSC
drug target
local anaesthetic (LIDOCAINE)
epilepsy
chronic pain
cardiac arrhythmia
81
Pain sensation and voltage-gated channels
VGSC play an important role in pain sensation (esp. NaV1.7-1.9)
one type (1.7) can cause in- and decreased pain
- PRIMARY ERYTHROMELALGIA: mutation in SCN9A cause e.g. lowering of threshhold potential
- PEPD: paroxysmal extreme pain, e.g. gof in SCN9A leads to no pore collapse
- CIPA: complete insensitivity to pain, e.g. no opening
82
primary erythromelalgia
usually painless stimuli (e.g. touch) are percieved as painful
cause e.g. mutation in SCN9A (NaV1.7) that cause lowering of threshhold for receptor-opening
83
PEPD
paroxysmal extreme pain disorder
caused by e.g. gof mutation in SCN9A that alters biophysical properties
e.g. no pore collapse
84
CIPA
complete insensitivity to pain
caused by e.g. SCN9A mutation that leads to no opening of NaV1.7
85
KV channels
types
4 subfamilies depending on ligand and structure (TM domains)
- Kir: K inward rectifying channels, 2TM
- K2P: 2 pore K channel, 4TM
- KCa: Ca gated K channel, 6-7TM
- KV: voltage gated K channel, esp. KV11.1 important
86
KV channels
structure
TETRAMER of 4 alpha-SU with 6TM regions each
- VOLTAGE SENSOR S1-4 with S4 positively charged
- PORE FORMATION by S5-6
- MODULATION by linker between dom 1&2
- INACTIVATION by linker between dom 3&4
87
KV channels
opening
like NaV channels
- IC positive charge pushes S4 outwards
- pore opens
- linker between domain 3&4 collapses into the pore
88
KV11.1
target of class II antiarrhythmics
mutations can lead to LQTS
mutations (SNPs) can be localized in RXR (ER retention motif) or influence glycosilation
every drug is screened against KV11.1 interaction --> could cause arrhythmia
89
CaV channels
three classes depending on their threshhold
activity is modified by kinases, GPCRs, etc
90
CaV channels
selectivity filter
towards K the size and Cl the charge
Na very similar -> 2 neg charges transmit ion to two other neg charges -> Na only one +
91
CaV channels
structure
- alpha1 SU as channel with 24 TM helices in 4 regions
- beta SU auxilliary
- alpha2delta SU for proper localization
92
CaV channels
drug target
- DHP: dihydropyridine, binds allosteric inactivated channel (modulator)
- VERAPAMIL: binds in pore and prevents ion flow (channel blocker)
93
DHP
dihydropyridine
binds allosteric to inactivated CaV
94
Verapamil
channel blocker for CaV
binds in pore
95
super agonist
more activation than original compoundu
96
full agonist
activation like original compound
97
partial agonist
activation less than original compound by e.g. only causing partial opening to a intermediate state
98
antagonist
no activation, but any basal activity is usually not prevented
99
inverse agonist
also inhibition of basal activity (less activity than when there is no ligand present)
100
allosteric modulators
change in activity by binding away from original binding site
can influence affinity or effficacy
101
competitive inhibition
drug competes with original compound since both bind the same binding site
102
reversible inhibition/activation
drug has same affinity as original compound and can therefore be displaced over time
103
irreversible inibition/activation
drug has increased affinity and cannot be displaced, new receptor/protein etc hs to be produced in order to regenerate
104
types of signal transmission
axodendritic
axosomatic
axoaxonic
105
EPSP generating sites
active zones, some synapses have one active zone, some have multiple
106
active zone
EPSP generating site, some synapses have one, some have more
107
electrical synapse
ion flow from one cell to the next via gap junctions
one gap junction are two connexons (6 connexins each) tethered by ionic interaction
negative charges witthin the gap junction prevent Cl- flow
108
types of NT
AA
amines
neuropeptides
109
NT
AA
glutamate
GABA
glycine
110
NT
amine
dopamine
serotonin
histamine
(nor-) epinephrine
Acetylcholine
111
NT
Neuropeptides
CCK
SP
NPY
TRH
VIP
SST
dynorphins, enkephalins
112
vesicular NT transporters
- VMATs: monoamines, 2H+
- VAChT: ACh, 2H+
- VGAT: GABA and glycine, nH+
- VGLUTs: glutamate, nH+
work because of H+ gradient (proton pump ATPase)
drug target as alternative to NT reuptake, not yet clinically used
113
VMATs
vesicular monoamine NT transporter
transport in exchange for 2H+
114
VAChT
vesicular ACh transporter
in exchange for 2H+
115
VGAT
vesicular GABA or glycine transporter
exchnage for nH+
116
VGLUTs
vesicular glutamate transporter
in exchange for nH+
117
vesicular NT transporters
drug target
alternative to targeting NT reuptake (e.g. SNRIs) but not yet clinically applied
118
NT-vesicle fusion
PRIMING: syntaxin 1A and SNAP-25 (tSNAREs) bind to Synaptobrevin (vSNARE) with Munc18 as intermediate
Ca2+ required for full zppering and membrane fusion
Ca2+ via CaV in close proximity (RIM, Munc , Rab and tSNAREs bound to CaV)
kiss & run or full fusion
119
NT-vesicle fusion
types and recycling
kiss and run or full fusion
recycling: ultra-fast endocytosis at kiss-an-run, otherwise clathrin mediated or bulk endocytosis
120
NT vesicle fusion
drug target
trageted by several toxins
Botolinum toxin (inhibition)
Tetanus toxin (GABA vesicles -> excitation)
121
NT release
drug targets (excitatory)
- NaV channels
- CaV channels (e.g. alpha2delta SU)
- vesicle surface proteins
- postsynaptic receptors
122
NT release
drug targets (inhibitory)
- GABA transaminase
- GAT1
- post-synaptic Cl channels
123
receptors monoamine neuron
VMAT
DAT/NET/SERT for reuptake
124
receptors acteylcholine neuron
VAChT
AChEsterase cleaves i synaptic cleft
ChT for choline reuptake
125
receptors GABA neuron
three-part synapse
VGAT
GAT1 for direct reuptake
GAT3 for glial reuptake
GABA transaminase for GABA to Glu
Glutamine synthase for Glu to Gln
SN1/SN2 for glial Gln export
SAT3 for Gln uptake in neuron
126
receptors glutamate neuron
three-part synapse
VGLUTs
GLT for direct reuptake
GLT/GLAST for glial reuptake
Glutamine synthase for Glu to Gln
SN1/SN2 for glial Gln export
SAT3 in neuron for Gln uptake
127
DAT
dopamine reuptake transporter
128
NET
norepinephrine reuptake transporter
129
SERT
serotonin reuptke transporter
130
ChT
choline transporter for choline reuptake
131
AChE
ACh esterase for cleavage ito acetat and choline
132
GAT1
GABA transporter for neuronal GABA reuptake
133
GAT3
GABA transporter for glial GABA reuptake
134
GABA transaminase
converts GABA to Glu
in glial cells important for GABA recovery
135
Glutamine synthase
converts Glu to Gln
in glial cells important for GABA and Glu recovery
136
SN1
transporter in glia cells for Gln export
137
SN2
transporter in glia cells for Gln export
138
SAT3
in neurons for Gln uptake
139
GLT
in neurons for direkt Glu reuptake
in glia cells (or GLAST) for glial reuptake
140
GLAST
in glia cells (or GLT) for Glu reuptake
141
NT reuptake
dependend on NA/K gradient (Na/K ATPase)
facilitated by NSS (neurotransmitter sodium symptorter)
LeuT for biogenic amines, GABA and glycine
EAAT for excitatory AA (Glu)
142
opening process EAAT
excitatory AA transport
outward open -> Glu and Na bind
outward occluded, inward occluded
inward open -> Glu and Na dissociate, K binds
reverse process -> K dissociates
143
three part synapse
pre-a dn post-synaptic neurons and glia cell
important in glutamatergic and GABAergic neurons for reuptake
144
NT reuptake transporter
drug target
ANTIDEPRESSANTS: SSRI, SNRIs
TIAGABINE: anticonvulsants, reduced GAT1 (prolonged GABA signalling)
PSYCHOSTIMULANTS: amphetamine, cocaine block DA transporter
145
amphetamine
blocks DAT -> reduced DA reuptake
146
cocaine
blocks DAT -> reduced DA reuptake
147
SSRIs, SNRIs
antidepressants
reduced serotonin reuptake (or norepinephrine) (SERT, NET)
148
Tiagabine
anticonvulsants
inhibit GAT1 -> reduced GABA reuptake
149
ionotrophic glutamate receptors
examples
AMPA
NMDA
kianate
150
ionotrophic glutamate recepors
structure
4SU form tetrameer
EC amino-terminal domain
EC ligand-binding domain
TM-domain: 3 alpha-helices (M1, M3-4) and loop (M2) as selectivity filter
151
AMPA receptor
ionotrophic glutamate recepor
conducts positive ions
Ca2+ conductance of GluA2 SU prevented by RNA-EDITING (Q to R --> argine is pos. charged)
152
NMDA receptor
ion flow blocked by Mg2+ binding in pore
IC pos. charge (Na from AMPA R) "kicks" Mg out
ion flow including Ca
Ca leads to signalling and more AMPA receptors (LTP)
153
long term potentiation
AMPA easier activated
if enough activated than Ca flow through NMDA receptors
Ca leads to more AMPA receptors
if once a signal was strong enough, the nxt time the signal does not be as strong
154
membrane localization of AMPA
interaction with several proteins
e.g. TARPgamma2 in ER, or PSD-95 on membrane (tethers to other proteins)
155
ionotrophic glutamate recepors
drug target
anti-epileptic drugs
- PMP (perampanel): stabalizes closed AMPA 8reduced ion flow)
- VALPORATE: targets NMDA
- FELBAMATE: targets NMDA
156
PMP
perampanel
anti-epileptic
stabalizes closed AMPA (reduced ion flow
157
Perampanel
PMP
anti-epileptic
stabalizes closed AMPA (reduced ion flow
158
Valporate
anti-epileptic
targets NMDA
159
Felbamate
anti-epileptic
targets NMDA
160
drug targeting AMPA
PMP (perampanel)
161
drug tageting NMDA
Valporate
Felbamate
162
TARPgamma2
protein binds to AMPA in ER
required for proper localization
163
PSD-95
protein, binds to AMPA in membrane
tethers it to other proteins in (synaptic) membrane
164
cys-loop receptors
examples
inhibitory: GlyR, GABA-A
excitatory: nAChR, 5HT3R
165
cys loop receptors
structure
PENTAMER, each SU has
EC amino-term domain
EC ligand-binding dom
TM dom: 4 alpha helices, M2 of all 5 forms pore
166
M2 of Cys-loop receptors vs ionotrophic glutamate receptors
glutamate rec: tetramer, M2 forms selectivity filter
cys-loop: pentamer, M2 forms pore
167
GlyR
ion, disease
cys-loop receptor (PENTAMER)
- Cl conducting
- disease relevant in fainting goat, startle disease, epilepsy
168
GlyR
conformations
cys-loop receptor
- open: all residues allow pore with r > 2A
- closed: L9 of M2 in pore
- inactivated: P2 of M2 in pore
169
GlyR
drug target
PTX (picrotoxin)
blocks GlyR -> hyperactivation due to desinhibition
170
GlyR
physiological circuit example
spinal cord reflex circuit: pain from stubbed toe lead to inhibition of flexor muscles and activation of extensor, opposite reaction on other leg for stabilization
171
GABA-A
structure
cys-loop receptor
2 alpha, 2 beta, 1 gamma (PENTAMER)
GABA binding site between alpha and beta SU (2 binding sites)
172
GABA-A
localization
synaptic: fast and short signal
extra-synaptic: longer but less strong signal
173
GABA-A
drug target
target for most anti-epileptic drugs (BENZODIAZEPINES)
- DIAZEPAM: allosteric moulator, increased activation probability
- PTX: picrotoxin, blocks pore and hyperactivation due to desinhibition
- ALP: alprazolam, allosteric modulator increases Cl flux
- PROPOFOL: general anaesthetic, fast acting
174
Picrotoxin
PTX
blocks pore of GABA-A and GlyR
leads to hyperactivation due to desinhibition
175
PTX
picrotoxin
blocks pore of GABA-A and GlyR
leads to hyperactivation due to desinhibition
176
Diazepam
Benzodiazepam
acts on GABA-A
allosteric moulator, increased activation probability
177
ALP
alprazolam
Benzodiazepine
acts on GABA-A
allosteric modulator increases Cl flux
178
Aprazolam
ALP
Benzodiazepine
acts on GABA-A
allosteric modulator increases Cl flux
179
Propofol
acts on GABA-A
general anaesthetic, fast acting
180
nAChR
excitatory cys-loop receptor (PENTAMER)
Na influx upon 2 ACh binding
primarily in muscle end plate
181
nAChR
drug target
depolarising: directly in nAChR, cause massive Na influx which prevents further activation after initial activation, e.g. succinylcholine
non-depolarising: can act on ACh rather than receptor, but CURARE is non-activating competitor to ACh and binds nAChR (muscle relaxans)
182
curare
poison that competitively binds nAChR in a non-activating fashion
used as muscle-relaxans in history
183
GPCRs
classes
Class A: rhodopsin receptor family (e.g. DA-receptors)
Class B: secretin receptor family (e.g GABA-B)
Class C: mGlu-like receptor family, can signal as monomers
184
G proteins
types
Gs: activate AC, more cAMP, more PKA
Gi: inhibit AC
Gq: activate PLC, IP3 and DAG from PIP2
185
G proteins
targets
AC: adenylyl cyclase, activating or inhibiting (Gs or Gi), more cAMP leads to more active PKA
PLC: IP3 and DAG from PIP2, IP3 increases IC Ca, DAG activates PKC and other
Ion channels: opens K (hyperpolarization), inhibits Ca (red. NT release)
PLA2: opens K and inhibits Ca channels
186
AC
adenylyl cyclase
target of Gs and Gi
more cAMP leads to more active PKA
187
PLC
phospholipase C
target of Gq
IP3 and DAG from PIP2 -> IP3 increases IC Ca, DAG activates PKC and other
188
ion channels and G proteins
can interact with each other
opens K (hyperpolarization)
inhibits Ca (red. NT release)
189
PLA2
phospholipase A2
target of G proteins, influences ion channels
opens K (hyperpolarization) and inhibits Ca (red. NT release)
190
desensitization of GPCRs
GRK phosphorylates GPCRs
- phosphorylation as internalisation signal and eventual lysosomal degradation
- process reversed by phosphotases
beta-arrestin can bind phosphorylated GPCR
- promotes endocytosis
- blocks GPCR signalling
191
GRK
G protein-coupled receptor kinase
phosphorylates GPCRs
- phosphorylation as internalisation signal and eventual lysosomal degradation
- process reversed by phosphotases
- phosphorylation facilitates beta-arrestin binding
192
beta-arrestin
modulation of GPCR activity
- binds phosphorylated GPCR (GRK)
- promotes endocytosis
- blocks GPCR signalling
193
dopamine receptors
GPCRs Class A
- D1-like: DRD1 and DRD5, Gs coupled
- D2-like: DRD2-4, Gi coupled
D2Sh: short, pre-synaptic involved in DA synthesis, storage and release
D2Lh: classic post-synaptic receptor
194
dopamine receptor
drug target
PRAMIPREXOLE: treatment of AD als alternitive to L-DOPA (to delay DOPA-induced dyskinesia), agonist for D3R
195
Pramiprexole
D3R agonist (DA receptor)
reatment of AD als alternitive to L-DOPA (to delay DOPA-induced dyskinesia)
196
drug as alternative to L-DOPA (AD)
pramiprexole
D3R agonist (DA receptor)
used to delay DOPA-induced dyskinesia
197
GABA-B
GPCR Class B
- functions as HETERODIMER with GB1 (ligand bindng) and GB2 (function)
- ligand binding leads to conformational shift (twisting and shift of TM domains) -> now G protein can interact
- Gi coupled, beta-gamma activate GIRK (K influx)
- target of Baclofen
198
GABA-B
drug target
BACLOFEN: muscle spasticity, allosteric modulator
off-label use for alcohol addicts (manages cravings)
199
Baclofen
GABA-B allosteric modulator
indicated for muscle spasticity
off-label use for alcohol addicts
200
