Receptor-effector coupling Flashcards
Second messengers are molecules that …….
brief definition
molecules that relay messages received at cell surface receptors to target molecules in the cytosol or in the nucleus
Principle of Amplification - G-proteins
Explain
Amplification
Activation of more than one G protein
Active G protein can interact with the effector enzyme for a duration that is sufficient to produce multiple product molecules
If this is a second messenger -> further amplification
Adenylate cyclase
- what it does - the pathway
- which protein targets it which inhibits it
- what breaks/ degrades it … bonus point - think of something which prevents this degradation
Adenylate cyclase
Target for active G proteins, activated by Gs (β adrenoceptors) and inhibited by Gi (m2AchR)
Produce cAMP from ATP
Activate cAMP-dependent protein kinase - PKA
Regulates specific enzymes through phosphorylation
Degraded by phosphodiesterases (inhibited by methylxanthines)
Intracellular calcium raise
- how
- G protein pathway
- Calmoduin role
- Decreasing cytosolic Ca2+ levels - is achieved how
Intracellular calcium raise
Release from intracellular stores (α1 adrenoceptors) or opening of Ca2+channels
Activation of phospholipase C (PLC)
PIP2-> IP3+ DAG- Gq
IP3releases intracellular calcium by binding to receptors
DAG activates protein kinase C (PKC) which phosphorylates specific targets
Role of calmodulin - 4 Ca2+bind to it activating it (subunit on myosin light chain kinase) -> muscle contraction
Reuptake of calcium by SERCA and extrusion from cell by PMCA and NCX
State what these abbreviations stand for
. DAG
. SERCA
. PLC
. PMCA
. NCX
DAG = Diacylglycerol
SERCA = SarcoEndoplasmic Reticulum Calcium ATPase
PLC = Phospholipase C
PMCA = plasma membrane Ca2+-ATPase
NCX = Sodium-calcium exchange
Intracellular calcium levels:
R…. l…. when calcium is released from intracellular stores
Calcium binds to ….., causing a conformational change and the formation of a ……. ….
Activates calcium pumps to store calcium in ER or pump out of cell
Binds to ….. which ….. m….. , allowing …. muscle contraction
Raised levels
calmodulin, calcium-calmodulin complex
MLCK - myosin light chain kinase
phosphorylates, myosin light chain
smooth
State
Gq protein and its effects:
Gq protein and its effects:
Stimulates phospholipase C which cleaves PIP2 into IP3 and DAG which act as additional second messengers
Classic mechanism of smooth muscle contraction after stimulation of⍺1 adrenoreceptors or M3 cholinergic receptors
IP3 stimulates receptors on ER/SR to promote opening of ligand-gated calcium channels- increases cytoplasmic calcium levels for muscle contraction and secretion
DAG activates protein kinase C (PKC)- increases secretion and intracellular processing
Elaborate on the cAMP pathway
The cAMP pathway:
Activated by many different stimuli: β-adrenoreceptors, glucagon receptors, H2 receptors, VIP receptors
Leads to an increase in protein kinase A (PKA) activity- cAMP binds and releases activated functional subunits
Continues until phosphodiesterase decreases cAMP levels, drugs that inhibit these enzymes (methylxanthines- used to treat asthma so smooth muscle relaxes) can cause greater effects
Elaborate on Control of adenylate cyclase by G-proteins:
Activation of Gs proteins (stimulatory) causes⍺-subunit to dissociate and bind to adenylate cyclase
Causes conformational change which increases adenylate cyclase activity so increased conversion of AMP to cyclic 3’-5’ AMP (cAMP)
Activation of Gi proteins (inhibitory) decreases adenylate cyclase activity and cause a lowering of cAMP levels, e.g. the muscarinic receptor (M2 and M4)
A large effect that receptors can have on cells is through the actions of second messengers, most commonly with GPCRs where activation of the receptor allows the exchange of GDP for GTP
This cleaves the⍺-GTP from the β-γ subunits
Process allows amplification as more G-proteins can be cleaved in this manner
Enjoy : )
