2.7 Adrenergic Physiology

Question 1

What is the adrenergic system

Answer 1

Adrenaline, (aka epinepherine) and noradrenaline (aka norepinepherine) and the adrenoreceptors that they act on

Question 2

What types of neurons are noradrenergic

Answer 2

Noradrenaline is used as the postganglionic neurotransmitter in the sympathetic nervous system

Question 3

Where are noradrenergic neurons and where do they project to

Answer 3

The cell bodies of these noradrenergic neurons are most prominent in the pons and the neurons project to the cortex, hippocampus, thalamus, hypothalamus, cerebellum and spinal cord.

Question 4

Give examples of what noradrenergic neurons are involved in

Answer 4

They are involved in control of blood pressure, sedation, analgesia and mood

Question 5

What hormone group are noradrenaline and adrenaline part of

Answer 5

Catecholamines. Synthesis of catecholamines occurs in sympathetic nerve varicosities

Question 6

What are the different intermediaries in the synthesis of adrenaline and what is the rate limiting step

Answer 6

tyrosine>DOPA>dopamine>noradrenaline>adrenaline

tyrosine to DOPA is the rate limiting step

Question 7

Where is adrenaline synthesised from noradrenaline

Answer 7

In chromaffin cells of the adrenal medulla

Question 8

Describe the steps involved in producing adrenaline from tyrosine

Answer 8

Tyrosine enters the adrenergic neuron along with Na+ via an aromatic L-amino acid symporter. In the neuron cytosol, tyrosine is converted to DOPA via tyrosine hydroxylase, DOPA us then converted to dopamin by DOPA decarboxylase. Dopamine then enters a vesicle via a VMAT antiporter (with H+ moving out), in the vesicle dopamine is synthesised into noradrenaline via dopamine b-hydroxylase. There is then Ca2+ dependent release of the noradrenaline from the vesicle into the synapse before some of the noradrenaline is taken back into the presynaptic membrane via a Na+ symporter. The noradrenaline (and adrenaline) can then interact with a and b adrenoreceptors on the pre and post synaptic membranes (a2 is an autoreceptor to mediate feedback inhibition on the pre and post synaptic membranes)

Question 9

Once adrenaline and noradrenaline have influenced the postsynaptic adrenoreceptors, what are the ways that the adrenaline synthesis response be terminated

Answer 9

• reuptake of the catecholamines into the presynaptic neuron
• metabolism of catecholamine to an inactive metabolite (by MAO or COMT enzymes)
• diffusion of catecholamine away from the synaptic cleft

Question 10

How would you classify adrenoreceptors

Answer 10

G protein linked and metabotropic

Question 11

What are the 5 types of adrenoreceptor

Answer 11

a1,a2,B1,B2,B3

Question 12

Which adrenoreceptors are on the presynaptic membrane and which are on the postsynaptic membrane

Answer 12

a2 is on the presynaptic and postsynaptic

a1, b1 and b2 are on the postsynaptic

b3 is not on the presynaptic or postsynaptic

Question 13

What does activation of a1 receptors cause

Answer 13

Contraction of smooth muscle, glycogenolysis in liver and K+ release in salivary glands

Question 14

What does activation of a2 receptors cause

Answer 14

In the presynaptic causes a decrease in noradrenaline release and in the postsynaptic causes a decrease in insulin release

Question 15

What does activation of B1 receptors cause

Answer 15

Activation of b1 receptors affects heart (increasing contractility and heart rate) and kidney (increasing angiotensin, increasing blood volume and total periphery resistance)

Question 16

What does activation of B2 receptors cause

Answer 16

Activation of b2 receptors causes smooth muscle relaxation and metabollic effects such as an increase in lipolysis, glucagon and liver glucose production

Question 17

What does activation of b3 receptors cause

Answer 17

smooth muscle relaxation, lipolysis and thermogenesis

Question 18

Describe adrenaline’s affinity for different adrenoreceptors

Answer 18

Adrenaline has a higher affinity for b receptors but can also have an affect on a receptors at high concentrations (e.g high doses of adrenaline is effective at treating anaphylaxis and is used for vasoconstriction)

Question 19

Describe noradrenalines affinity for different adrenoceptors

Answer 19

Noradrenaline has a high affinity for a1 and b1 but low affinity for b2

Question 20

Give some selective direct acting (aka sympathomimetic) adrenergic agonist drugs

Answer 20

• a1 agonists- increases peripheral resistance and smooth muscle contraction e.g phenylephrine
• a2 agonists- reduces noradrenaline release and reduces smooth muscle contraction e.g clonidine
• b1 agonists- inotropic effects increasing contractility and cardiac output e.g dobutamine
• b2 agonists- treating asthma by relaxing bronchial muscle e.g albuterol
• b3 agonists- treats overactive bladder and promotes lypolysis e.g mirabegron

Question 21

Give some direct acting (aka sympathomimetic) non selective adrenergic agonist drugs

Answer 21

• non selective general a agonists- oxymetaxoline (nasal decongestant)
• non selective general b agonists- isoproterenol (for emergency arrhythmias and bronchospasms)

Question 22

Give some indirect acting adrenergic agonist drugs

Answer 22

• inhibitors of catecholamine storage - reserpine and tyramine
• inhibitors of catecholamine reuptake - cocaine and imipramine
• inhibitors of catecholamine metabolism - selegiline

Question 23

Give some specific adrenergic antagonist drugs

Answer 23

• a1 antagonists- prazosin used to treat hypertension
• a2 antagonists- yohimbine used for male impotence
• b1 antagonists- atenolol used to treat hypertension and angina
• b2 antagonists- blockade of b2 receptors is clinically undesirable, but butoxamine has still been discovered as one

Question 24

Give some non specific adrenergic antagonist drugs

Answer 24

• non specific a antagonist general effects- prevents vasoconstriction, decreases blood pressure and causes baroreceptor reflex (e.g phentolamine)
• non specific b antagonist general effects- decreases heart rate and myocardial contractility (e.g propranolol)