GPCR

Question 0

What is Gs?

Answer 0

Ga is bound to GDP and is part of a,b,y complex
Activation at a receptor causes conformational changes which exposes the Ga binding site to the cytosol, where GTP>GDP
Ga releases GDP a and binds to GTP a causing another conformational change
Ga-GTP complex dissociated from by and can now bind to AC
AC increases cAMP and this activates PKA

Question 1

What is Gi?

Answer 1

• mops up any Gs subunits
• decreases any Gs effects
• inhibits AC
• inhibits VGCC and increases effluent of potassium, slowing polarisation
  Causes decrease in heart rate
  Causes contraction is VSMC

Question 2

What is Gq?

Answer 2

Ga is bound to GDP and is part of a,b,y complex
Activation at a receptor causes conformational changes which exposes the Ga binding site to the cytosol, where GTP>GDP
Ga releases GDP a and binds to GTP a causing another conformational change
Ga-GTP complex dissociated from by and can now bind to phospholipase c
Membrane bound pip2 is hydrolysed by PLC and broken into DAG and IP3
IP3 releases calcium stored in SRI
DAG activates PKC which opens calcium channels allowing influx
Both cause increase in internal calcium, which then binds to cal modulin, which activates MLCK which phosphorylation MLC. Actin myosin interaction can now occur, contraction occurs .

Question 3

What receptors are there in cardiac muscle?

Answer 3

Muscarinic - M2 GI
Inhibits AC, decrease in rate
Inhibits VGCC a, decrease in polarisation causes decrease in rate

Beta - 1 2 and 3 Gs
Stimulates AC
Increases contraction
Switches off potassium channel= increased excitability = increase in rate

Question 4

What is a1?

Answer 4

Found in VSMC
Adrenergic 
Gq
NA>A
Contraction
IP3 releases calcium stored in SRI
DAG activates PKC which opens calcium channels allowing influx
Both cause increase in internal calcium, which then binds to cal modulin, which activates MLCK which phosphorylation MLC. Actin myosin interaction can now occur, contraction occurs .

Question 5

What is a2?

Answer 5

VSMC not locate presynaptically
Gi
NA>A
Contraction
Inhibition of AC, less cAMP, less PKA.
PKA inhibits MLCK, so as there is less PKA there is more MLCK phosphorylation of MLCK, actin/myosin interaction can now occur.
In VSMC PKA prevents MLCK a from phosphorylation

Presynaptically located a2

A2 receptors located presynaptically on the synapses where the nt noradrenaline is released from act as inhibitory self regulation receptors.

On stimulation, they cause inhibition of AC in the synaptic bulb, which reduces cAMP. CAMP promotes ca2+ influx in response to membrane depolarrisation, which then promotes the release of noradrenaline into the post synaptic space. With a decrease of cAMP there is a reduction of release noradrenaline.

Noradrenaline is the main regulator of vascular cells, and an increase of noradrenaline causes contraction. As this causes a reduction of NA there will be a relaxation of blood vessels, and a decrease in blood pressure.

Because it is a sympathetic pathway it can cause constipation and dry mouth as well as sedation.