Exam 2: Monoamines Flashcards
2 types of monoamines - examples in each
indolamines (serotonin)
catecholamines (dopamine, norepinephrine, epinephrine)
what neurotransmitters share a biosynthetic pathway
catecholamines (dopamine, epinephrine, norepinephrine
- all start with tyrosine
catecholamine synthesis begins with the amino acid…
tyrosine
what is the rate limiting enzyme for catecholamine sysnthesis?
tyrosine hydroxylase (TH) - amount of dopamine depends on amount and activity of TH
what converts dopa to dopamine
aromatic amino acid decarboxylase (AADC)
what converts dopamine to norepinephrine
dopamine B-hydroxylase (DBH)
what are catecholamines transported into vesicles by?
vesicular monoamine transporters (VMAT)
what happens if DA and NE are not protected in vesicles?
they get broken down and levels drop causing sedation and depression
VMAT blocker
Reserpine
- produces state of depression
- used in animals
2 mechanisms of catecholamine inactivation
reuptake and enzymatic degradation
reuptake of catecholamines
DA transporter and NE transporter bring DA and NE back into the cell
- molecules then repackages into vesicles or broken down
what do antidepressants usually block?
NET and SERT
what does cocaine inhibit?
reuptake of DA, NE, 5-HT
get build up in the synapse
enzymatic degradation of catecholamines
COMT and MAO (MAOB)
Dopamine metabolite in humans
homovanillic acid (HVA)
NE metabolite
MHPG (3-methoxyl-4-hydroxy-phenylglycol in brain
VMA (vanillymandelic acid) in PNS
2 families of dopamine receptors
all metabotropic
D1 family and D2 family
D1 family of receptors
excitatory - inc adenylyl cyclase
includes D1 and D5
D2 family of receptors
inhibitory - reduces adenylyl cyclase
D2, D3, D4
hyperpolarization
DA autoreceptor
inhibitory - opens K+ channels, K+ exits cell
D2 receptor
presynaptic
neurons that use dopamine are called
dopaminergic
dopamine neuron cell bodies located in what 3 brain regions
ventral tegmental area
hypothalamus
substantia nigra
4 dopamine pathways
mesolimbic dopamine system
mesocortical dopamine ssytem
tuberoinfundibular dopamine system
nigrostriatal dopamine system
mesolimbic dopamine system
cell bodies in VTA project to the nucleus accumbens (ventral striatum)
mesocortical dopamine system
cell bodies in VTA and project to the cerebral cortex
tuberoinfundibular dopamine system
cell bodies in hypothalamus and axons project to pituitary (prolactin)
nigrostriatal dopamine system
cell bodies in substantia nigra axons project to the striatum
cells producing NE are referred to as
noradrenergic
where are cell bodies of NE located?
locus coeruleus in the pons
lateral tegmental system in the midbrain
axons project all over forebrain
NE systems modulate
mood, arousal, and sexual behavior
what is NE?
a neurotransmitter and a hormone
NE as a hormone?
released from adrenal glands and travels in bloodstream to target organs
- CANNOT cross BBB
release of NE effects on SNS
inc BP, inc HR, dec digestion, dilation of blood vessels to skeletal muscles, heart and brain
all NE receptors are
metabotropic
alpha NE receptors
a1-excitatory
a2-inhibitory - autoreceptor
beta NE receptors
B1,2,3 all excitatory
serotonin is an
indolamine
most cell bodies of serotonin are located in
raphe nuclei (brainstem) and axons project through brain
what is serotonin implicated in
sleep states, mood, sexual behavior, anxiety, hunger, aggression
Prozac
increases serotonin activity
serotonin is synthesized from what amino acid
tryptophan
rate limiting step of serotonin
tryptophan hydroxylase (TPH) converting tryptophan to 5-hydroxytryptophan (5-HTP)
what converts 5-HTP to 5-HT
AADC (aromatic amino acid decarboxylase)
how is serotonin transported into vesicles
VMAT2
Inactivation of serotonin: reuptake
reuptake by serotonin transporter (SERT)
SSRis (selective serotonin reuptake inhibitors)
antidepressants
increase the amount of serotonin available
serotonin inactivation: enzymatic breakdown
breakdown of 5-HT catalyzed by MAO-A
metabolite: 5-hydroxyindoleacetic acid (5-HIAA)
ionotropic serotonin receptor
5-HT3
inhibitory serotonin receptors
5-HT1
5-HT5
serotonin autoreceptor
5-HT1A
terminal autoreceptors- directly inhibit release
somatodendritic autoreceptors-indirectly inhibit release by slowing rate of neuron firing
Inhibitory 5-HT1AR expression
hippocampus, septum, amygdala, dorsal raphe, striatum
agonists reduce anxiety and pain
Inhibitory 5-HT1BR expression
pain perception
constricts blood vessels and blocks pain signals to ease pain in migraine sufferers
agonists reduce food intake - anorexia
excitatory 5-HT2AR expression
large amount in cerebral cortex
contribute to hallucinogenic effects of drugs (LSD)
