Download Slide 1

Overview of links between sections 9 to 13
From signal perception (by a GPCR) to response (28/11 -13)
Starting point: GPCR & a/b/g complex
P.M.
GDP
b ga
Ligand: e.g. fMet, adrenalin, “smell”, light, etc.
P.M.
GDP
b ga
b
+
GTP
a
GDP GTP
The trimeric G-protein complex is recruited to the receptor
 GDP/GTP exchange (the receptor acts as a GEF)
1
Examples of down-stream GPCR effectors
Organ specific
Most cells
GTP
aq
PLC-b
GTP
as
GTP
ai
Adenylyl cyclase
GTP
aolf
GTP
at
cGMP-phosphodiesterase
ADRENALIN: cAMP synthesis in liver and muscle cells  Protein kinase A
SMELL: cAMP synthesis in olfactory cells
 Ion channels
LIGTH: cGMP hydrolysis in cells of the retina
 Ion channels
2
Transmission of signals through CNS & PNS
De-polarization or hyper-polarization (electrical signals)
Synaptic signaling (electrical signals & neurotransmitters)
: Electrical signal
Control of smooth muscle relaxation
Default state = contraction
: Electrical signal
Ca2+
1. Acetylcholine (synaptic signaling)
2. Endothelial cells produce NO
3. Diffusion of NO to smooth muscle cells
(paracrine signal)
4. Activation of guanylyl cyclase  cGMP
5. Activation of an “in ward” Ca2+ pump
6. Decreased cytosolic [Ca2+]
7. Actin-myosin filaments slides apart
smooth muscle relaxation
8. Increased blood flow
Ca2+
Response = relaxation
4
Neuromuscular junction
Somatic motor neurons project their axons to skeletal muscles.
The interface between motor neurons and skeletal muscles is a
specialized synapse termed neuromuscular junction.
1.
2.
3.
4.
5.
Acetylcholine release at the neuromuscular junction
Depolarization of muscle cells (-70 mV ~0 mV)
Opening of Ca2+ channels
Increased cytosolic Ca2+
Troponin mediated translocation of tropomyosin
Response = contraction
Tropomyosin
Tropomyosin
Tropomyosin
Tropomyosin
Ca2+
The Hypothalamic-Pituitary-Adrenal system
Physical work/stress
Two distinct signals to AG
SNS signal
ACTH secretion
GPCR (AG medulla):
Adrenalin secretion
into the blood
GPCR (AG cortex):
Cortisol secretion
into the blood
(lipolysis etc etc)
Neuroendocrine
integration
GPCR (liver and muscles)
adenylyl cyclase  cAMP
Protein kinase A
Glycogen phosphorylase
AG: Adrenal Gland
Glycogen breakdown
ACTH: AdrenoCorticoTropic Hormone, SNS: Sympathetic Nervous System
6