Adrenergic Effects

Question 1

What are the two types of Adrenergic Receptors?

Answer 1

• α-receptors, where noradrenaline is more potent than adrenaline is more potent than isoprenaline
• β-receptors, where isoprenaline is more potent than adrenaline is more potent than noradrenaline

Question 2

What are the three types of adrenoreceptors?

Answer 2

• α1-adrenoreceptors
• α2-adrenoreceptors
• β-adrenoreceptors

Question 3

List the five adrenoreceptors that we’ve learnt, which enzyme they activate, and some of their agonists and antagonists.

Answer 3

• α-1 ADRENORECEPTOR
  Enzyme: Phospholipase C (αGq/11)
  Agonist: Phenylephrine, Oxymetazoline
  Antagonist: Prazosin, Doxazosin, Tamsulosin (1a)
• α-2 ADRENORECEPTOR
  Enzyme: Adenylate Cyclase (αGi)
  Agonist: Clonidine
  Antagonist: Yohimbine
• β-1 ADRENORECEPTOR
  Enzyme: Adenylate Cyclase (αGs)
  Agonist: Dobutamine
  Antagonist: Atenolol
• β-2 ADRENORECEPTOR
  Enzyme: Adenylate Cyclase (αGs)
  Agonist: Salbutamol, Salmeterol, Clenbuterol
  Antagonist: Propranolol
• β-3 ADRENORECEPTOR
  Enzyme: Adenylate Cyclase (αGs)
  Agonist: Mirabegron
  Antagonist: -

Question 4

Describe the effects α1 adrenoreceptors have, ie. what tissue they affect and how it is done (G-protein subunit related).

Answer 4

α1-adrenoreceptors contract vascular smooth muscle (contraction of seminal vesicles, iris muscles for dilation, and pilomotor muscles)

The α1-adrenoreceptor, as we know, has a αGq/11 subunit. Ths activates Phospholipase C, which converts PIP2 to IP3 and DAG. The IP3 stimulates the release of Ca2+ from the SR, leading to increased contraction.

Question 5

Describe how the α2 adrenoreceptor works (G-protein subunit related), and what its effect is.

Answer 5

The α2 adrenoreceptor has a αGi subunit, which works on Adenylate Cyclase, although negatively. This means that less cAMP will be made, so less PKA will be activated. PKA tends to sensitise calcium channels to voltage, so less calcium is released with lowered levels of PKA.

α2 adrenoreceptors inhibit transmitter release.

Question 6

Describe the β1 adrenoreceptor cardiac effects.

Answer 6

When activated:

• heart rate is increased (positive chronotropy)
• conduction velocity is increased (positive dromotropy)
• contractility is increased (positive inotropy)
• rate of myocyte relaxation (positive lusitropy)

Sympathetic adrenergic nerves innervate the SAN, the AVN, the conduction pathways and myocytes in the heart. The nerves release noradrenaline.

Question 7

Describe the change in the contraction graph when β1 adrenoreceptors are activated, and what causes these changes.

Answer 7

For the contraction graph, the contractions are bigger because we have more Ca2+ present, but they are briefer because there is now better Ca2+ reuptake.

Question 8

Describe how β1 adrenoreceptor work (G-protein related).

Answer 8

The β1 adrenoreceptor has a αGs subunit, so it positively activates Adenylate Cyclase. This leads to an increase in cAMP, which leads to an increase in activated PKA. The PKA then opens up Ca2+ and K+ channels. the K+ influx hyperpolarises the cell, which leads to the opening of the Na+/K+ pacemaker channels to help stabilise the cell polarity.

Question 9

What effect do β1/2 adrenoreceptors have on smooth muscle?

Answer 9

They cause the relaxation of smooth muscle, especially airways. It also affects skeletal muscle vasculature, and also coronary and cerebral blood vessels.

This is why β2 agonists are used in asthma inhalers to relax inflamed bronchi.

Question 10

Describe the role of β1-adrenoreceptors in the kidneys.

Answer 10

It affects the Juxtaglomerular Apparatus (JGA). It’s located between the afferent and efferent renal arteries.
It increases renin release. Renin is used to convert inactive Angiotensinogen into its active form, Angiotensinogen I.

Question 11

What happens when β3 adrenoreceptors are activated?

Answer 11

An increase in stimulation of β3 adrenoreceptors increases lipolysis in adipocytes.

Question 12

Name some uses of adrenoceptor agonists.

Answer 12

• EYE DROPS: Ephedrine/ Brimonidine
• NASAL DECONGESTANT: Phenylephrine/ Ephedrine
• PROLONGATION OF LOCAL ANAESTHETIC ACTION: Adrenaline
• ASTHMA INHALERS: Salbutamol
• CARDIAC STIMULANT: Adrenaline/ Dobutamine
• ANTI-OBESITY: BRL37344 in development
• ACUTE ANAPHYLAXIS (EG. BEE STING): Adrenaline
• PREMATURE LABOUR: β agonists
• OVERACTIVE BLADDER: β3 agonist, Mirabegron

Question 13

Name some uses of adrenoceptor blockers.

Answer 13

• HEART: Atenolol
• KIDNEYS: Atenolol
• ADRENAL GLAND TUMOUR: Phenoxybenzamine
• URINATION: α1a-selective (eg. Tamsulosin), which relaxes prostate and bladder neck muscles

Question 14

NEW: What are postganglionic varcosities?

Answer 14

You get varicosties instead of sympathetic nerve endings. Varicosities looks like beads on a string. They contain synaptic vesicles, and release neurotransmitters to the rceptors on the smooth muscle sarcolemma.