Receptors 2 Flashcards
What receptors do most small molecules chemical mediators/neurotransmitters use?
Type 1 and type 2
Ligand gated ion channels and G-protein coupled receptors
What receptor detects hormones?
G-protein coupled receptors
How many transmembrane domains does a GPCR have?
7
What is an orphan GPCR?
Where the extracellular ligand they respond to is unidentified
How do GPCRs regulate effector proteins?
Via a heterotrimeric GTP binding protein
(1 alpha, 1 beta and 1 gamma subunit)
What is the structure of an alpha subunit? What is its function?
GDP bound molecule
Defined different G proteins
What is the structure of beta and gamma subunits?
The beta and gamma subunits come as a pair
Between which domains does the G protein bind?
Between the 5th and 6th domain
Can 1 G protein be used by more than 1 receptor?
Yes as different G protein subunits interact with different GPCRs and effectors
How does signal transduction occur in GPCRs?
A ligand binds to the GPCR which causes a conformational change (between receptor 5 and 6 on alpha)
The affinity of GDP decreases and is replaced by GTP which binds to the alpha and activates it.
Therefore, beta and gamma wont bind to the receptor and stimulate other effectors.
How does signal transduction terminate in GPCRs?
The alpha unit (enzyme GTPase) hydrolyses GTP to GDP,
This binds to alpha subunit and returns it back to its original state
What are 2 effector proteins? With examples
Ion channels (voltage gated, ligand gated, G protein gated)
Enzymes (adenylyl cyclase, phospholipase C)
What is a second messenger?
Small diffusible molecules that spread signals
Not membrane bound
Explain the effect of Ga(s) (stimulatory) on adenylyl cyclase
Increases adenylyl cyclase
Increases second messenger cAMP
Activated protein kinase A
Explain the effect of Ga(i) (inhibitory) on adenylyl cyclase
Decreased adenylyl cyclase
Decreased second messenger cAMP
Deactivated protein kinase A
What is the main role of cAMP? Example
Regulating the activity of other proteins involved in signal transduction.
Increases protein kinase A activity
Explain the mechanism of cAMP increasing PKA activity.
cAMP binds to regulatory subunits inducing a conformational change which reduces their affinity for catalytic subunits.
The complex dissociates and the catalytic subunits are free to catalyse phosphorylation of protein substrates.
What is the role of PKA?
Phosphorylates downstream effectors and regulates their activity
Can both alpha and betagamma subunits interact with effectors?
Yes they both can
How to beta-gamma G protein subunits interact with effectors?
They interact indirectly with ion channels
Describe how opioid receptors act via Gi proteins.
They increase GIRK permeability (potassium channel)
So more K+ leaves the cell and the cell becomes more negative.
Therefore, less action potential firing and less pain transmission
How do alpha G protein subunits interact with effectors?
Leads to second messengers
Describe the amplification of signaling through GPCR regulated second messengers.
Transmitters activates the receptor->
The receptor activates a G protein ->
G protein stimulates adenylyl cyclase to convert ATP to cAMP->
cAMP activates PKA which phosphorylates L potassium channels.
What is phospholipase C?
An enzyme effector modulated by G proteins
Describe the effect of Ga(q) on phospholipase C.
Activates phospholipase C ->
Activates IP3 which activates a receptor on er membrane and DAG ->
This signals the release of Ca2+ from er and increases PKC
How is smooth muscle contraction and GPCRs linked?
GPCRs coupled to Gq proteins and PLC signalling stimulate smooth muscle contraction.
Ca2+ released helps convert Myosin to Myosin P which causes a contraction
What is the function of Gs?
Activates adenylyl cyclase
Activates Ca2+ channels
What is the function of Gi?
Inhibits adenylyl cyclase
Activates K+ channels
What is the function of Gq?
Activates phospholipase C
