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MP222 > Adrenoceptor signalling > Flashcards

Adrenoceptor signalling Flashcards

1
Q

what is the most important characteristic of GPCR

A

They have seven transmembrane alpha helixes

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2
Q

what are g-proteins

A

specialised proteins able to bind to GDP and GTP

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3
Q

what are the 3 subunits of a g protein?

A

alpha
beta
gamma

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4
Q

What is the process of a g-protein binding to gpcrs

A

1) ligand binds to gpcr
2)gpcr undergoes conformational change
3) alpha subunit changes GDP for GTP
4) alpha subunit dissociates and regulates target proteins
5) target protein relays signals via 2nd messenger
6) GTP hydrolysed to GDP

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5
Q

what is a signalling pathway?

A

an intracellular biochemical pathway which links the receptor to the cellular (physiological) outcomes

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6
Q

what are the three ways gpcrs can be classified?

A

Gq - alpha 1
Gi - alpha 2
Gs - beta

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7
Q

what effect does subunit Gq have on alpha 1 receptor?

A

results in activation of phospholipase C, promotes conversion of PIP2 -> IP3 and DAG
-> IP3 results in an increase in intracellular calcium (from ER)
-> leading to smooth muscle contraction

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8
Q

what effect does Gi subunit have on alpha 2 receptor?

A
  • Inhibits adenylyl cyclase
  • Never allows conversion of ATP to cAMP
  • inhibits calcium coming into the cell
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9
Q

what effect does GS have on beta receptor?

A

Stimulates adenylyl cyclase which promotes the conversion of ATP to cAMP
- results in heart muscle contraction , smooth muscle relaxation, glycogenolysis

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10
Q

what does an increase in cAMP result in?

A

increased calcium
increase in contraction

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11
Q

how does B2 receptors result in relaxation of airway vessels?

A

Adenylyl cyclase is stimulated which promotes conversion of ATP to cAMP
This results in inhibition of calcium release
Leading to smooth muscle relaxation

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12
Q

where is the alpha 2 adrenoceptor in relation to the NA release site and what is it activated by ?

A

Close to NA site
Activated by neuronal and circulating NA

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13
Q

where is the alpha 2 adrenoceptor in relation to the NA releasing site and what is it activated by?

A

Distant from site
Activated by circulating NA

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14
Q

What is the Go protein?

A
  • Belongs to Gi/Go subfamily of g-proteins
  • a number of gpcrs transmit stimuli to intracellular effectors through Go
  • Go regulates several cellular effectors, including ion channels, enzymes
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15
Q

where is alpha 2 in the Gi/Go negative feedback pathway?

A

presynaptic cells

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16
Q

where is Go predominant?

A

In nervous tissue

17
Q

What happens during exocytosis in the Gi/Go pathway?

A

gets the vesicle out of the nerve terminal which requires calcium

18
Q

What effect does the drop of calcium in the Gi/Go pathway do?

A

releases noradrenaline - negative feedback

19
Q

What is the same action that muscarinic M2 receptors have on the SA node?

A

Alpha 2 effect on channels (K and Ca) via Go
Gi/Go is how the heart is dampened down/slowed down

20
Q

how does an increase in stroke volume and HR have an effect on arterial bp

A

increase in CO
Increase in volume entering arteries
Increase in arterial blood volume
Increase in arterial bp

21
Q

what effect does an increase in blood viscosity and decrease in arteriolar diameter have on arterial bp?

A

Increase in peripheral resistance
Decrease of volume of blood leaving arteries
Increase in arterial blood volume
Increase in arterial bp

22
Q

what do selective alpha 1 adrenergic antagonists do?

A

block the binding of noradrenaline to the smooth muscle receptors which results in vasodilation which lowers bp
- decrease in vascular tone (PVR)
- no change in HR or CO
eg. doxazosin, prazosin

23
Q

what can non-selective alpha blockers do?

A

Block alpha 1 and alpha 2 receptors
- causes vasodilation by blocking alpha 1
- most alpha 2 receptors are on presynaptic nerve endings - results in more noradrenaline release ( can stimulate beta 1 receptors on heart and cause tachycardia or arrithymias)

24
Q

what are examples of B1 antagonists?

A

atenolol
metoprolol
bisoprolol

25
Q

what’s an example of a B2 antagonist?

A

butoxamine

26
Q

what are examples of non-selective beta antagonists?

A

carvedilol
propranolol
sotalol
timolol

27
Q

what is the effect of B1 adrenoceptors on the heart?

A

+ve chronotropy - SA node (effect of rate or timing)
+ve inotropy - force of contraction (cardiac muscle)
Increase in cardiac output

28
Q

what is the affect of beta 1 adrenoceptors on smooth muscle?

A

GI tract - relaxation
Fat - lipolysis: tryglyceride fat stores - fatty acids
Kidney - increase in renin release which increases BP

29
Q

How do the kidneys work to reduce BP

A

Beta 1 adrenoreceptors causes renin release
- angiotensin converting enzyme causes angiotensin I and II release
- aldosterone released
- decreases release of sodium and water from the kidneys (decreases secretions) Results in increased blood volume (retention of water) which increases bp

MP222 (11 decks)

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