Adrenoceptors

Question 1

What receptors detect noradrenaline from the sympathetic nervous system?

Answer 1

Adrenoreceptors:
Alpha
Beta

Question 2

what is the agonist potency order for the alpha adrenoreceptors comparing noradrenaline, adrenaline and isoprenaline?

Answer 2

Alpha 1:
Noradrenaline > adrenaline&raquo_space; isoprenaline

Alpha 2:
Adrenaline > Noradrenaline&raquo_space; Isoprenaline

Question 3

what is the agonist potency order for the beta adrenoreceptors comparing noradrenaline, adrenaline and isoprenaline?

Answer 3

Beta 1:
isoprenaline > noradrenaline > adrenaline

Beta 2:
isoprenaline > adrenaline > noradrenaline

Beta 3:
isoprenaline > noradrenaline = adrenaline

Question 4

what is the structure of adrenoreceptors?

Answer 4

All adrenergic receptors are part of the family of G proteincoupled receptors (metabotropic receptors)

Recruit intracellular proteins, known as G proteins, in order to produce their cellular effects

Integral membrane protein

Single polypeptide chain: 400 - 500 amino acids

Extracellular N-terminus, intracellular C-terminus

7 transmembrane α helices

Binding site buried within a cleft between the α helices

Question 5

How do alpha 1 adrenoreceptors lead to downstream signalling?

Answer 5

1. Noradrenaline binds to its alpha 1 receptor.
2. A change takes place in the Gq-protein where GDP is converted to GTP.
3. This leads to the alpha subunit of the G-protein dissociating from the beta-gamma complex.
4. The alpha subunit can diffuse in the membrane to interact with its target protein phospholipase C.
5. Phospholipase C acts on PIP2 membrane phospholipid which produces IP3 and DAG.
6. IP3 binds to the IP3 receptors on the surface of the ER and opens Ca ion channels leading to Ca release.

Question 6

How do alpha 2 adrenoreceptors lead to downstream signalling?

Answer 6

Noradrenaline binds to its alpha 2 receptor.

1. A change takes place in the Gi-protein where GDP is converted to GTP.
2. This leads to the alpha subunit of the G-protein dissociating from the beta-gamma complex.
3. The alpha subunit can diffuse in the membrane to interact with its target protein adenyl cyclase.
4. The Gi-protein inhibits adenyl cyclase
5. which leads to decreased cAMP levels and thus less activity of PKA
6. Hence decreased phosphorylation of intracellular proteins.
7. Produces effects of inhibition of neurotransmitter release.

Question 7

give an example of an alpha 2 adrenoreceptor antagonist?

Answer 7

Yohimbine - used for treatment of sexual dysfunction.

Question 8

How do beta adrenoreceptors lead to downstream signalling?

Answer 8

Noradrenaline binds to the beta adrenoreceptors.
1. This recruits Gs-protein
2. The Gs (G-protein) is converted from its GDP to GTP form
3. The alpha subunit dissociates and goes to activate the protein adenyl cyclase.
4. This leads to:
increased cAMP levels
increased activity of PKA
increased phosphorylation of intracellular proteins.
Produces the effect of relaxation of smooth muscle.

Question 9

How can we target organs for drugs?

Answer 9

The 5 adrenoreceptors act upon different organs.

Question 10

What is the function of adrenoreceptors on the heart?

Answer 10

Beta 1 adrenoreceptors:
SAN - increased heart rate 
AVN - increased conduction velocity 
Atria - increased contractility 
Ventricles - increased contractility and enhance automaticity.

Question 11

what adrenoreceptors are found in blood vessels and what are their affects on the smooth muscle.

Answer 11

alpha 1 (2) - constriction
Beta 2 - dilation

Question 12

what adrenoreceptors are found in bronchi and what are their affects on the smooth muscle.

Answer 12

Beta 2 - dilation

Question 13

what adrenoreceptors are found in GIT and what are their affects on the smooth muscle.

Answer 13

Alpha 1, alpha 2 - contraction of sphincters

Beta 2 - relax

Question 14

what adrenoreceptors are found in uterus and what are their affects on the smooth muscle.

Answer 14

alpha 1 - contract

beta 2 - relax

Question 15

what adrenoreceptors are found in bladder and what are their affects on the smooth muscle.

Answer 15

Beta 3

Question 16

What would be the effect of agonists (noradrenaline, adrenaline and isprenaline) on the cardiovascular system?

Answer 16

Noradrenaline - increased peripheral resistance to increase blood pressure

Question 17

What are some adrenoreceptors agonists

Answer 17

α1 - phenylephrine

α2 - clonidine
β1 - dobutamine
β2 - salbutamol - terbutaline - salmeterol
β3 -mirabegron

Question 18

What are some adrenoreceptor antagonists?

Answer 18

α1 - prazosin - doxazosin

α2 - yohimbine - idazoxan

β1 - atenolol - metoprolol

β2 - butoxamine

Question 19

What is the function of adrenaline as an adrenoreceptor agonist?

Answer 19

activates both the alpha and beta agonist

used in cardiac arrest (to help restore cardiac rhythm)

Question 20

What is the function of Dobutamine as an adrenoreceptor agonist?

Answer 20

Selective B1 receptor agonist.

Used in cardiogenic shock (acute heart failure)

Question 21

What is the function of Salbutamol as an adrenoreceptor agonist?

Answer 21

Selective B2 receptor agonist

Used in asthma

Question 22

What is the function of Mirabegron as an adrenoreceptor agonist?

Answer 22

Selective B3 receptor agonist.

Treatment of overactive bladder syndrome (OAB)

Question 23

What is the function of Phenylephrine as an adrenoreceptor agonist?

Answer 23

Selective alpha 1 receptor agonist

Used for nasal decongestion

Question 24

What are some uses of alpha adrenoreceptor antagonists?

Answer 24

Hypertension
Benign prostatic hypertrophy
Phaeochromocytoma

Question 25

What are some uses of beta adrenoreceptor antagonists?

Answer 25

Cariovascular (hypertension, angina)

Glaucoma

Question 26

What are the adverse effects of Beta adrenoreceptors antagonists

Answer 26

Bronchoconstriction
worsening of cardiac failure 
bradycardia 
heart block 
hypoglycaemia 
physical fatigue 
cold extremities 
bad dreams