OCB03-2009 NORADRENALINE Flashcards
What type of function do α-adrenergic receptors have?
Excitatory or inhibitory
What type of function do β-adrenergic receptors have?
Excitatory
What CNS functions is NA important in?
Arousal
Central blood pressure regulation
Mood control
What are the two major nuclei containing noradrenergic neurons?
Locus coeruleus
Caudal raphe nuclei
Where is the locus coeruleus found?
Midbrain
Where are the caudal raphe nuclei found?
Near brainstem
Where do noradrenergic neurons from the locus coeruleus project to?
Frontal cortex
Thalamus
Hypothalamus
Limbic system
Cerebellum
Where do noradrenergic neurons from the caudal raphe nuclei project to?
Ascend to amygdala
Descend to spinal cord
How is NA formed?
Dopamine –> NA by dopamine-β-hydroxylase in vesicles
Where is dopamine-β-hydroxylase found?
In vesicles
What is the pathway of NA degradation in neurons?
NA –> dihydroxymandelic acid by MAOa
Dihydroxymandelic acid –> methoxyhydroxymandelic acid by COMT
What is the pathway of NA degradation in glial cells?
NA –> normetanephrine by COMT
Normetanephrine –> methoxyhydroxymandelic acid by MAOa
What can be measured to determine NA activity in the CNS?
Measure methoxyhydroxymandelic acid in urine
What does VMA mean?
Methoxyhydroxymandelic acid (vanillylmandelic acid)
How is NA removed from the synapse?
NET into neurons
ENT into glial cells
What does NET mean?
Norepinephrine transporter
What is the function of the presynaptic α2-receptors?
Inhibits NT release and inhibits voltage-gated Ca channels
What happens when α1-receptors are activated?
Gq
PLC activated to increase IP3 and DAG
Increases intracellular Ca++
What happens when postsynaptic α2-receptors are activated?
Gi
Adenylyl cyclase inhibited and K channel open and voltage-gated Ca channels close
K+ efflux = re/hyperpolarisation
What G protein are the β-adrenoceptors coupled to?
Gs
What receptors does isoprenaline act on?
Agonist for β1/2
What is isoprenaline used to treat?
Asthma
What receptors does dobutamine act on?
Agonist for β1
What is dobutamine used to treat?
Cardiogenic shock
What receptors does salbutamol act on?
Agonist for β2
What types of drugs are used to treat asthma?
β2 agonists
What receptors does phenylephrine act on?
Agonist for α1
What is phenylephrine used to treat?
Nasal congestion
What receptors does clonidine act on?
Agonist for α2
What is clonodine used to treat?
Hypertension
Migraine
High intraocular pressure
Menopause flushing
What receptors does phentolamine act on?
Antagonist of α1/2
What receptors does prazocin act on?
Antagonist of α1
What is prazocin used to treat?
Hypertension
What receptors does propanolol act on?
Antagonist for β1/2
What is propanolol used to treat?
Angina
Hypertension
Dysrhythmias
Anxiety
Tremor
What receptors does metoprolol act on?
Antagonist of β1
What is metoprolol used to treat?
Angina
Hypertension
Dysrhythmias
How does amphetamine or methylphenidate affect NA transmission and what is the result of this?
Displace NA from vesicles and inhibit MAO to increase NA release (leakage)
Addictive, stimulant; psychoses
Calming in ADHD
Narcolepsy
Appetite suppressant
How does cocaine affect NA transmission and what is the result of this?
Inhibits NET (main action on DAT)
Addictive, stimulant
How do tricyclic antidepressants/NSRIs/SNRIs affect NA transmission?
Inhibit NET
What is ephedrine used to treat?
Nasal decongestant (increases NA release in CNS)
How do MAO inhibitors affect NA transmission? What can they be used to treat?
Decreased NA metabolism
Treat depression
