L10: Adrenergic Transmission

Question 1

What is noradrenaline?

Answer 1

The chemical transmitter of the sympathetic nervous system.

Question 2

What are catecholamines?

Answer 2

1. Noradrenaline.
2. Adrenaline.
3. Dopamine.

Question 3

What are the sites of the release of catecholamines?

Answer 3

1- All postganglionic sympathetic fibers except those supplying skin, skeletal ms blood vessels, and sweat glands.

2- Some synapses in CNS.

3- Suprarenal medulla: adrenaline (80%) and noradrenaline (20%).

Question 4

How is catecholamine synthesized?

Answer 4

• Noradrenaline is derived from tyrosine amino acids.
• Synthesis begins in the cytoplasm of terminal nerve endings and is completed in vesicles present in adrenergic nerve fibers.
• Synthesis occurs in the chromaffin cells of SRM and in the CNS neurons.

 In liver:
• Phenylalanine - hydroxylation ——> tyrosine.

 In axoplasm of adrenergic nerve fiber:

• Tyrosine - hydroxylation ——> DOPA - decarboxylation ——> dopamine

 In adrenergic vesicles at nerve ending: Transport of dopamine. • Dopamine - +OH ——> Noradrenaline.

 In SRM and CNS neurons: this reaction goes one step to form adrenaline. Noradrenaline - +CH3 ——> Adrenaline

Question 5

Where is dopamine present in higher conc. Than noradrenaline?

Answer 5

In basal ganglia of the brain

Question 6

Where are catecholamines stored?

Answer 6

• NA is stored inside the nerve terminals in tiny vesicles (1000 molecules or more).
• But some molecules are found free in the cytoplasm.
• In the adrenal medulla, adrenaline and NA are stored in the form of granules in the
  chromaffin cells.

Question 7

How is catecholamine released?

Answer 7

• when the action potential reaches the axon terminal it opens the voltage-gated Ca+2 channels → Ca2+ influx →increase Ca2+ level → move the vesicles toward the membrane and fuse with it → vesicles rupture and empty their content outside nerve fiber NA cross the cleft (10-30 nm) & bind to its receptors on effector organ.
• Stimulation of Symp. preganglionic nerve fibers relaying on chromaffin cells in SRM causes adrenaline and NA release.

Question 8

What is the mechanism of action of Noradrenaline?

Answer 8

When NA binds with its receptors on the postsynaptic membrane, it leads to :

1. change of cell membrane permeability to various ions. It either:
   ➢ ↑es membrane permeability to Na and Ca → ↑ed Na and Ca influx → depolarization (stimulation).
   ➢ ↑es membrane permeability to K and Cl → ↑ed K and Cl influx → hyperpolarization (inhibition)
2. Activation of adenyl cyclase → conversion of ATP into cAMP→ initiates many intracellular activities.

Question 9

How is noradrenaline removed?

Answer 9

Once, NA produces its action, it is rapidly removed in three different ways:

• Neuronal uptake (85 %)

• NA is actively reuptaken into the adrenergic nerve end where it is stored in the vesicles or oxidized by monoamine oxidase (MAO).

• Extra neuronal uptake (15 %)
  • NA is inactivated by catechol-o-methyl transferase (COMT).
• Excretion in urine
  • Small amount of NA escapes enzymatic destruction and is excreted in urine (conjugated with glucuronic acid)

Question 10

Compare between MOA and COMT in terms of:

Name: 
Site of uptake:
Type of process: 
Amount removed:
Sites:

Answer 10

Mono-amino-oxidase
Catecholamine o- methyltransferase

Neuronal.
Extra –neuronal.

Produce oxidation
Produce methylation (then Excretion by glucuration)

Removal of 85% of adrenaline.
Removal of 15% of adrenaline.

-Present in mitochondria of
adrenergic fibers, liver, and kidney (ALK)
-Present in all tissues especially the kidney
and brain (KB)

Question 11

What is the definition of adrenergic receptors?

Answer 11

adrenergic receptors are receptors that respond to NA and adrenaline.

Question 12

What is the classification of adrenergic receptors?

Answer 12

1. α adrenergic receptors: subclassified into (α 1: excitatory and α 2: inhibitory)
   • They are equally sensitive to adrenaline and NA.
2. β adrenergic receptors: subclassified into (β 1 , β 2 , β 3 , β 4 , β 5 )

• β1:
o Are sensitive to both norepinephrine and epinephrine
o Are more sensitive than the α1 receptors

• β2:
o Are more sensitive to epinephrine than to norepinephrine.
o Are more sensitive to epinephrine than the α1 receptors.

N.B
➢ β3 receptors: located in the adipose tissues → increase lipolysis.
➢ β4 and β5 receptors: under research.

Question 13

What are the sites of alpha 1 receptors?

Answer 13

-Are postsynaptic receptors located on smooth ms of blood vessels in the skin and splanchnic regions, the GIT and bladder sphincters, and dilator pupillae ms of the iris and piloerector ms

Question 14

What is the mechanism of action of alpha 1 receptors?

Answer 14

Are G-protein coupled receptors that activate phospholipase C, and increase in inositol 1,4,5-triphosphate (IP3) and intracellular [Ca2+] to make contraction or excitation

Question 15

What are the physiological actions of alpha 1 receptors?

Answer 15

Mainly excitatory:-

➢ Vasoconstriction
➢ Contraction of piloerector muscle.
➢ Contraction of splenic capsule.
➢ Contraction of the seminal vesicle, ejaculatory duct.
➢ Contraction of bladder & intestinal sphincters.
➢ Adrenergic sweating in the palm.

-Inhibitory effects as
➢ Intestinal relaxation.
➢ Inhibition of insulin secretion.

Question 16

What are the sites of alpha 2 receptors?

Answer 16

1. Presynaptic: On presynaptic sympathetic nerve ending and on ganglion cells (autoreceptors).
2. Postsynaptic in some effector organs e.g. platelets, fat cells, and the walls of the GI tract (heteroreceptors)

Question 17

What is the MOA of alpha 2 receptors?

Answer 17

Inhibit or even block intracellular cAMP.

Question 18

What are the physiological actions of alpha 2 receptors?

Answer 18

-mainly inhibitory

a) Presynaptic
➢ negative feedback inhibition of more NA release.

b) Postsynaptic 
➢ CNS inhibition.
➢ Peripheral platelet aggregation 
➢ Vasoconstriction of some vessels. 
➢ Decreased lipolysis.
➢ Decreased insulin secretion.

Question 19

What is the site of beta 1 receptors?

Answer 19

1- Heart.
2- Juxtaglomerular cells.
3- Intestine and fat cells

Question 20

What is the MOA of beta 1 receptors?

Answer 20

Activate adenyl cyclase →↑intracellular cAMP within the cell, initiating many intracellular activities.

Question 21

What are the physiological actions of beta 1 receptors?

Answer 21

-Mainly excitatory:-
➢ Increased all cardiac properties (increased heart rate, increased contraction force, increased conduction velocity, increased excitability).
➢ Increased renin secretion
➢ Increased lipolysis.  
➢ Decreased platelet aggregation

Question 22

What are the sites of beta 2 receptors?

Answer 22

Widely distributed in the body.

Question 23

What is the MOA of beta 2 receptors?

Answer 23

Activate adenyl cyclase →↑intracellular cAMP within the cell, initiating many intracellular activities.

Question 24

What are the physiological actions of beta 2 receptors?

Answer 24

Mainly inhibitory (GIF)
➢ Smooth muscle relaxation e.g. intestinal, bladder, uterine relaxation, vasodilatation, bronchodilatation.
➢ Stimulation of liver and muscle glycogenolysis.
➢ Stimulation of pancreatic insulin secretion.
➢ Increased blood fibrinogen level

Question 25

what contributes to the vasoconstriction of vessels?

Answer 25

Alpha 1 and alpha 2 but alpha 1 mainly

Question 26

What dec and inc lipolysis respectively?

Answer 26

Alpha 2

Beta 1 and beta 3

Question 27

What affects platelet aggregation?

Answer 27

Alpha 2 inc

Beta 1 dec