31
3
bound, opsins form functional photoreceptors, the rhodopsins. Here, upon absorption of
one photon, the 11-cis conformation of retinal changes to all-trans, inducing the intracellular signal transduction cascades that allow light perception in photoreceptor cells of the
retina. The photoreceptor cells synapse with neurons, and via the optic nerve, all visual
information is transmitted to the brain. This is why carrots are good for our eyes.
How are GPCRs in animals coupled with their transducers to evoke cellular responses
after ligand binding? The first answer to this question came from test tube assays carried
out by Rall and Sutherland in 1962 (Rall and Sutherland 1962). They measured an increase
b b
Phosphorylation of
enzymes or CREB
ER
lumen
Cytoplasm
c
Endocannabinoids
Acetylcholine, adrenaline, noradrenaline, adenosine,
endocannabinoids, enkephalin, serotonin
a
4
3
2
1
7
6
5
. Fig. 3.1 Schematic representation of a G-protein-coupled receptor (GPCR, serpentine or seventransmembrane domain receptor). a Intracellular signalling at GPCRs via G S /G i . Adenylyl cyclase (AC) is
the target enzyme for G S /G i and regulates cAMP levels. b Protein kinase A (PKA) is activated by cAMP and
in turn phosphorylates substrates including the transcriptional activator cAMP response element binding protein (CREB). c Intracellular GPCR signalling via Gq. Phospholipase C (PLC) is the target enzyme for
Gq and hydrolyses membrane phosphoinositols producing inositol-3-phosphate (IP3) and diacylglycerol
(DAG). DAG remains in the membrane and is a second messenger involved in activation of protein kinase
C and a precursor for endocannabinoid synthesis. IP3 opens Ca 2+ -channels in the membrane of the
endoplasmatic reticulum (ER)
3.1 · G-Protein-Coupled Receptors
3
bound, opsins form functional photoreceptors, the rhodopsins. Here, upon absorption of
one photon, the 11-cis conformation of retinal changes to all-trans, inducing the intracellular signal transduction cascades that allow light perception in photoreceptor cells of the
retina. The photoreceptor cells synapse with neurons, and via the optic nerve, all visual
information is transmitted to the brain. This is why carrots are good for our eyes.
How are GPCRs in animals coupled with their transducers to evoke cellular responses
after ligand binding? The first answer to this question came from test tube assays carried
out by Rall and Sutherland in 1962 (Rall and Sutherland 1962). They measured an increase
b b
Phosphorylation of
enzymes or CREB
ER
lumen
Cytoplasm
c
Endocannabinoids
Acetylcholine, adrenaline, noradrenaline, adenosine,
endocannabinoids, enkephalin, serotonin
a
4
3
2
1
7
6
5
. Fig. 3.1 Schematic representation of a G-protein-coupled receptor (GPCR, serpentine or seventransmembrane domain receptor). a Intracellular signalling at GPCRs via G S /G i . Adenylyl cyclase (AC) is
the target enzyme for G S /G i and regulates cAMP levels. b Protein kinase A (PKA) is activated by cAMP and
in turn phosphorylates substrates including the transcriptional activator cAMP response element binding protein (CREB). c Intracellular GPCR signalling via Gq. Phospholipase C (PLC) is the target enzyme for
Gq and hydrolyses membrane phosphoinositols producing inositol-3-phosphate (IP3) and diacylglycerol
(DAG). DAG remains in the membrane and is a second messenger involved in activation of protein kinase
C and a precursor for endocannabinoid synthesis. IP3 opens Ca 2+ -channels in the membrane of the
endoplasmatic reticulum (ER)
3.1 · G-Protein-Coupled Receptors