Norepinephrine, Epinephrine, Serotonin, Histamine

norepinephrine

• influences sleep & wakefulneess

• influences attention

• influences feeding behavior

• localized in locus coeruleus (brain stem)

• also in sympathetic ganglion cells of the periphery

where is norepinephrine localized?

locus coeruleus

epinephrine

• acts similar to norepinephrine

• localized in the medullary epinephrine neurons

• involved in visceral functions

• produced in adrenal medulla

where is epinephrine produced?

adrenal medulla

which NT is involved in visceral functions?

epinephrine

where is epinephrine localized?

medullary epinephrine neurons

what enzyme is present in adrenergic neurons to make epinephrine?

PNMT

what enzyme is present in noradrenergic enzymes that adds an OH to dopamine?

dopamine-beta hydroxylase

serotonin, norepinephrine, and epinephrine are loaded into vesicles by….

VMAT (vesicular monoamine transporter)

what recycles norepinephrine and also dopamine?

NET (Norepinephrine Transporter)

• brings NE back into the cell

what enzymes breakdown norepinephrine?

MAO and COMT (same as DA)

are adrenergic receptors ionotropic or metabotropic?

metabotropic

epinephrine and norepinephrine act on _________ receptors

the same

serotonin

• regulates sleep and wakefulness

• important in anxiety and depression

• localized primarily in the raphe nuclei & pons

where is serotonin localized?

1. raphe nuclei (brainstem)

2. pons

what amino acid is serotonin made from?

tryptophan

what NT regulates sleep and wakefulness and is important in anxiety and depression?

serotonin

rate limiting step of serotonin synthesis

tryptophan hydroxylase (1st step)

where is serotonin (5-HT) converted to melatonin?

pineal gland

in the pineal gland, serotonin (5-HT) is converted to:

melatonin

how is serotonin involved in regulating sleep/wakefulness?

it is converted to melatonin in the pineal gland

what packages serotonin?

VMAT

what recycles serotonin (5-HT)?

SERT (Serotonin Transporter)

where do SSRIs act?

SERT

what breaks down serotonin?

MAO in neurons and synapse (primarily MAOb)

most receptors are metabotropic, but ______ is ionotropic

5-HT3

5-HT3 is the ionly ionitropic receptor. it is a _________ channel that excites ________

cation / post-synaptic

amphetamines target what 3 things?

1. NET

2. SERT

3. DAT

amphetamines target NET, SERT, and DET, leading to…

increased release of all NT

• treatment of ADHD

what is the effect of amphetamines on channels?

• cause NET, SERT, and DAT to operate in reverse, increasing NT concentration in the synapse

• inhibit MAO-b, causing an increase in intracellular NT

• inhibit VMAT-2, preventing NT from getting into vesicle so more NT is in cytoplasm and able to be released by the transporter

goal of SSRIs

increase concentration of serotonin in synapse

2 allelles of serotonin transporter

1. long (increases expression, healthy)

2. short (less transporter)

long serotonin transporter allele

• increases serotonin transporter expression

• strong reuptake

• healthy serotonin system

• good baseline of production/reuptake

short serotonin transporter

• makes less transporter

• less serotonin in synapse

• less receptors

short allele of serotonin transporter ______ risk for depression

increases

variants of ______ gene are associated with increased risk for mood and neuropsychiatric disorders

COMT

2 potential alleles of COMT

1. Val-158

2. MET-158

Val-158 COMT allele

• more active

• high dopamine degrading activity

• low dopamine concentration in synapse (especially PFC)

MET-158 allele for COMT

• low dopamine degrading activity

• increase in dopamine concentration in synapse (espcially PFC)

COMT variants may impact…

chronic pain

how is histamine synthesized?

from histidine, by histidine decarboxylase

histamine mediates…

arousal and attention

functions of histamine

• arousal and attention

• important in vestibular system (antagonists help with motion sickness)

• may influence brain blood flow

• important in allergic response (antihistamines)

what breaks down histamine?

1. histamine methyltransferase

2. MAO

histamine receptors are all…

G-protein coupled

where is histamine localized?

tuberomammillary nucleus of hypothalamus

postsynaptic effects of histamine include…

1. postsynaptic excitation

2. plasticity

postsynaptic targets of histamine may be…

1. Gs coupled

2. Gq coupled

3. ion channels

4. NMDA receptors

what packages histamine into vesicles?

VMAT

is histamine an autoreceptor?

yes → presynaptic inhibition