in the Teaching Material of Medical Biotechnology Masters P rogrammes at the University of Pécs and at the University of Debrecen Identification number TÁMOP412081A20090011 ID: 311813
Download Presentation The PPT/PDF document "Manifestation of Novel Social Challenges..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
Slide1
Manifestation of Novel Social Challenges of the European Union
in the Teaching Material of
Medical Biotechnology Master’s
P
rogrammes
at the
University of
Pécs
and at the University of Debrecen
Identification
number
: TÁMOP-4.1.2-08/1/A-2009-0011Slide2
Signaling in the nervous system
Tímea Berki and Ferenc Boldizsár
Signal transduction
Manifestation of Novel Social Challenges of the European Union
in the Teaching Material of
Medical Biotechnology Master’s
P
rogrammes
at the
University of Pécs and at the University of Debrecen
Identification number
: TÁMOP-4.1.2-08/1/A-2009-0011Slide3
Presynaptic
neuron
(
axon
terminal
)
Postsynaptic neuron
Neurotransmitter molecule
NT transporter
Synaptic vesicles
Voltage-gated sodium channel
GPCR (modulatory)
Ligand-gated ion channel(direct excitation or inhibition)
+
+
Synapse
between
two
neurons-
neurotransmissionSlide4
Mechanism
of
neurotransmissionSynaptic
vesicles
contain a
neurotransmitter (NT) and release it when their membranes fuse with the outer cell membrane.
Neurotransmitter molecules cross the synaptic cleft and bind to receptors known as ligand-gated ion channels (LGICs) and G-protein–coupled receptors (GPCRs
) on the postsynaptic neuron.GPCRs on the presynaptic neuron’s axon terminal alter the function
of voltage-gated ion channels and modulate neurotransmitter release.Neurotransmitter transporters remove neurotransmitter molecules from the synaptic
cleft so that they can be repackaged into vesiclesSlide5
Receptors
Ionotropi
c
(
ion-channel linked
)Metabotropic(use second messengers)
GABAA, GABAC, iGluGlycine,Serotonin, Nicotinic Ach,P2X
GABAB, mGlu, Adrenaline, Noradrenaline, Glucagon, FSH, LH, TSH, ADH, parathormone,
growth-factors, cytokinesReceptorsSlide6
Receptor -
ligand
interaction
Receptor
properties
LigandsLigand binds in the core region of
the 7 transmembrane helices11-cis-retinal (in rhodopsin)AcetylcholineCatecholaminesBiogenic amines (histamine,
serotonine, etc.)Nucleosides and nucleotidesLeukotrienes, prostaglandins, prostacyclins, ThromboxanesShort
peptide ligands bind partially in the core region and to the
external loopsPeptide hormones (ACTH, glucagon, growth hormone)Parathyroid
hormone, calcitoninLigands make several contacts with the N-terminal segment
and the external loopshypothalamic glycoprotein releasing factors (TRH, GnRH)Induce
an extensive reorganization of an extended N-terminal segmentMetabotropic receptors for neurotransmitters
(such as GABA and glutamate)Ca2+-sensing receptors, for example on parathyroid cells, thyroidal C-cells
(which
secrete
calcitonin) and on
the
renal Juxtaglomerular apparatusProteinase activated
receptorsReceptors for
thrombin amd thrypsinSlide7
Ion channel receptors
Cys-loop receptors:
pentameric
structure, 4 transmembrane (TM) regions/subunit
Acetylcholin (Ach) Nicotinic R – Na+ channel GABAA, GABAC, Glycine – Cl- channels (inhibitory role in CNS) Glutamate-activated cationic channels: (excitatory role in CNS), tetrameric
stucture, 3 TM regions/subunitiGlu ATP-gated channels: 3 homologous subunits, 2 TM regions/subunitP2X purinoreceptorSlide8
7-transmembrane-spanning receptors
(7-TM)Class A:
Rhodopsin
-likeClass B: Secretin
familyClass C: Glutamate and GABA (metabotropic)FrizzledAdhesion familySlide9
7
-
TM ligands
Class A
Prostaglandins
ThromboxaneSerotonineDopamineHistamineCatecholaminesAch (M)
RhodopsinMelatoninChemokinesBradykininSomatostatinOpioidvasopressin
Class BGlucagonGnRHPTHCRH
Class CGlutamateGABASweet tastesSecretin
FrizzledWntHedgehogBitter tastes
AdhesionChondroitin-sulfateSlide10
Nicotinic Ach receptor
P
ore formed from 5 subunits: 2a
,
b, g, d
Opening: the 2a units are distorted Desensitization: in the open conformation the b, g, d subunits become phosphorylated by Protein kinase A and CSlide11
Neurotransmission
Ions
GTP
a
Receptor
G-protein
is
activated
Effector
protein
Intracellular
messengers
G-protein subunits or intracellular
messengers modulate ion channels
Neurotransmitter
GTP
g
b
a
Cytoplasm
Plasma membrane
Neurotransmitter
Ion channel
Cytoplasm
Plasma
membraneSlide12
Acetylcholine
Ions pass through
the pore
Binding site for
neurotransmitter
Change in intracellular
ion contrentration
Five
assembled
subunits
(
2×
+
3×
)
of
nAChR
Extracellular
Cytoplasmic
COOH
NH
2
TM
1
TM
2
TM
3
TM
4
Extracellular
Cytoplasmic
Ligand
binding
site
Four
hydrophobic
transmembrane
domain
(TM1-4)
One subunit of nAChR
Nicotinic
acetylcholine
receptor (
nAChR
)
O
N
O
CH
3
H
3
C
H
3
C
CH
3
Acetylcholine
↑
PLC
↑ [Ca
2+
]
↑ MAP
kinases
↓ M current
↓ Voltage-operated
Ca
2+
channels
↓ Adenylyl cyclase
↑ MAP kinases
↑ GIRK channels
Extracellular
Cytoplasmic
Muscarinic
acetylcholine
receptor (
mAChR
)
Acetylcholine
M1, M3, M5
M2, M4
TM
1
TM
3
TM
5
TM
7
TM
2
TM
4
TM
6
Gq/11
Gi/0
TM
1
TM
3
TM
5
TM
7
TM
2
TM
4
TM
6Slide13
Adrenergic
receptors
Receptor
Gi
2
Inhibition
of
transmitter
release
Ca
2+
Adenylyl
cyclase
ATP
cAMP
Smooth muscle
relaxation
Gq
1
Smooth
muscle
contraction
Ca
2+
Phospholipase
C
PIP
2
IP
3
DAG
Gs
Heart
muscle
contraction
Smooth
muscle
relaxation
Glycogenolysis
Adenylyl
cyclase
ATP
cAMP
Adrenalin,
NoradrenalinSlide14
Blocking the neuromuscular transmission
a-
Bungarotoxin
:
S
nake venom (Bungarus multicinctus) Binds to the N-Ach receptor and inactivatesCurare (
tubocurarin): In South American plants Strychnos toxifera and Chondrodendron tomentosum Indians use
as arrow poisonCurare binds to the same place on the N-Ach receptor than Achetylcholin BUT channel doesn’t openCauses
paralysis of breathing musclesUsed as muscle relaxant in anaesthesiaAntidote: Acetylcholinesterase inhibitors