GPCR basics Flashcards
GPCRs are
7 transmmemrbane receptors, which sense molecules on the outside of the cell and activate inside signal transactions pathways and cellular responses
ligands
hormones, NT, light sensitive compounds
3 families of GPCR
A, B, C
A-
rhodopsin- sensitive to light, activates G protein transducer Gt to activate the hototransduction pathway
B-
secretin/ glucagon receptor family e.g. peptide hormones
C-
metabotropic glutamate family e.g. GABAA and glutamte
mGluRs….
- modulation of synaptic transmission and neuronal excitability throughout the CNS
- high levels in cerebellum and thalamus
Group 1 mGlu receptors
couples to PLC and intracellular calcium signalling
activity of G proteins is regulated by
factors which control their ability to bind to and hydrolyse GTP to GDP
when GTp is bound
on
when GDP bound
off
G proteins are activated by
GPCR
G proteins are made up of
alpha, beta and gamma subunits ( beta-gamma complex)
activation of G proteins process
- When GPCR binds to a signal molecule, the receptor is activated and changes shape, thereby allowing it to bind to an inactive G protein
- When this occurs, GTP displaces GDP which activates the G protein
- After transduction the G protein functions as a GTPase and hydrolyses the bound GTP which causes a phosphate group to fall off
- Regenerating GDP and inactivates G protein and the cycle repeats
GalphaS controls which pathway
the cAMP dependent pathwat
GalphaS and the cAMp dependent pathway
1)Gs alpha subunit stimulated G protein complex exchanges GDP to GTP and is released form the complex
2) the activated Gs alpha submit binds to and activates adenyl cyclase, which catalyses the conversion of ATP to cAMP
3) this increases in conc of the second messenger cAMP leads to activation of PKA
4) PKA enzyme is only activated when cAMP is present
5)
responses mediated by cAMP
heart rate, cortisol section, breakdown of glycogen and fat
PKA
protein kinase A
protein kinase A is also known as
cAMP dependent enzyme because it gets activated only when cAMP is present
cAMP pathways can..
activate enzymes and emulate gene expression (if this pathway is not controlled, it may lead to hyper-proliferation, which can contribute to cancer)
GalphaI mainly
inhibits cAMP dependent pathway by inhibiting adenylate cyclase activity, decrease
GalphaI
1) when Gi gets activated they release activated G-protein beta-gamma submits from inactive heterotrimeric G protein complexes
2) Gbeta-gamma interacts with GIRK channels to open them
3) they become more permeable to K+
4) hyperpolarization of the cell
GIRK
gated, inwardly rectifying potassium channels
GalphaI receptors mainly found
on the heart and the brain
opioids target
GalphaI
GalphaQ is involved in
activation of phospholipase C (PLC)
GalphaQ
1) Gq activates PLC
2) PLC hydrolyses PIP2 to IP3 and DAG
3) DAG is a second messenger which activates PKC
4) IP3 acts on calcium channels to release calcium from store dn phosphorylation of some proteins
GalphaQ receptors (7)
- serotonergic receptors
- Alpha-1 adrenergic receptors
- Vasopressin type 1 receptors
- Angiotensin II receptor type 1
- Histamine
- mGluR- Group 1
- M1, M2,M3 muscarinic receptors
Summary of Gs
receptors: -beta adrenergic receptors, glucagon, histamine, serotonin singling pathway - increase adenyl cylase - increase in cAMP - excitatory effect
Summary of Gi
receptors: - alpha2 adrenergic receptors -mAchR -opiopd -serontin Singling pathway - inhibits adenylyl cycle -decrease in cAMP - opens GIRK channels (cardiac K+ channels) -hyperpolarisation -decrease in heart rate
Summary of Gq
receptors:
- mAchR
- serotonin
signaling pathway:
- activation of PLC
- PIP2- IP3 and DAG (PLC activation)
- increase in ca2+
