2.7 Adrenergic Physiology Flashcards
What is the adrenergic system
Adrenaline, (aka epinepherine) and noradrenaline (aka norepinepherine) and the adrenoreceptors that they act on
What types of neurons are noradrenergic
Noradrenaline is used as the postganglionic neurotransmitter in the sympathetic nervous system
Where are noradrenergic neurons and where do they project to
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.
Give examples of what noradrenergic neurons are involved in
They are involved in control of blood pressure, sedation, analgesia and mood
What hormone group are noradrenaline and adrenaline part of
Catecholamines. Synthesis of catecholamines occurs in sympathetic nerve varicosities
What are the different intermediaries in the synthesis of adrenaline and what is the rate limiting step
tyrosine>DOPA>dopamine>noradrenaline>adrenaline
tyrosine to DOPA is the rate limiting step
Where is adrenaline synthesised from noradrenaline
In chromaffin cells of the adrenal medulla
Describe the steps involved in producing adrenaline from tyrosine
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)
Once adrenaline and noradrenaline have influenced the postsynaptic adrenoreceptors, what are the ways that the adrenaline synthesis response be terminated
- 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
How would you classify adrenoreceptors
G protein linked and metabotropic
What are the 5 types of adrenoreceptor
a1,a2,B1,B2,B3
Which adrenoreceptors are on the presynaptic membrane and which are on the postsynaptic membrane
a2 is on the presynaptic and postsynaptic
a1, b1 and b2 are on the postsynaptic
b3 is not on the presynaptic or postsynaptic
What does activation of a1 receptors cause
Contraction of smooth muscle, glycogenolysis in liver and K+ release in salivary glands
What does activation of a2 receptors cause
In the presynaptic causes a decrease in noradrenaline release and in the postsynaptic causes a decrease in insulin release
What does activation of B1 receptors cause
Activation of b1 receptors affects heart (increasing contractility and heart rate) and kidney (increasing angiotensin, increasing blood volume and total periphery resistance)
What does activation of B2 receptors cause
Activation of b2 receptors causes smooth muscle relaxation and metabollic effects such as an increase in lipolysis, glucagon and liver glucose production
What does activation of b3 receptors cause
smooth muscle relaxation, lipolysis and thermogenesis
Describe adrenaline’s affinity for different adrenoreceptors
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)
Describe noradrenalines affinity for different adrenoceptors
Noradrenaline has a high affinity for a1 and b1 but low affinity for b2
Give some selective direct acting (aka sympathomimetic) adrenergic agonist drugs
- 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
Give some direct acting (aka sympathomimetic) non selective adrenergic agonist drugs
- non selective general a agonists- oxymetaxoline (nasal decongestant)
- non selective general b agonists- isoproterenol (for emergency arrhythmias and bronchospasms)
Give some indirect acting adrenergic agonist drugs
- inhibitors of catecholamine storage - reserpine and tyramine
- inhibitors of catecholamine reuptake - cocaine and imipramine
- inhibitors of catecholamine metabolism - selegiline
Give some specific adrenergic antagonist drugs
- 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
Give some non specific adrenergic antagonist drugs
- 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)
