2.6 - Epinephrine and Norepinephrine

dopamine (ref. NE and EPI)

transported in vesicles and converted into NE and EPI in neurons containing appropriate enzymes

norepinephrine (NE) synthesis

oxidized from dopamine by dopamine beta-hydroxylase in cytosol (limited by supply of dopamine)

NE transport

- requires active cotransport

- stored in synaptic vesicles by VMAT1 or 2 (ion transport H+ for NE)

- reuptake from synaptic cleft by NE transporter → terminates signaling 

Epinephrine (epi)

- NT of sympathetic NS

- aka “adrenaline”

EPI synthesis

- methylation from NE by phenylethanolamine N-methyltransferase (PNMT)

- stress indirectly increases synthesis

- rxn rate limited by supply of NE

epi transport

storage and reuptake is performed by VMAT and NET as described w/ NE

adrenergic receptors

- NE and EPI

- all metabotropic 7 transmembrane proteins GPCR-class receptor

NE and EPI uptake inhibitors

block amine transporters to ↑ NT, ADHD medication Atomoxetine

NE and EPI false transmitters

packaged like and replace NT, but weak (or no) receptor affinity

EPI and NE degradation

metabolized by MOA and catechol-O-methyl transferase (COMT)

alpha-1 receptors (A,B, and D)

Gq; excitatory (↑ AC)

alpha-2 receptors (A, B, and C)

Gi; inhibitory (↓ AC)

beta receptors (1, 2, and 3)

Gs, excitatory (↑ AC)

EPI in CNS

- located in medullary reticular formation

- involved in stress response, anxiety + memory

EPI in ANS

“flight or fight” = ↑ HR, respiration, glycogenolysis, muscle contraction

locus coeruleus (NE pons-medulla tract)

regulate BP via alpha-2A centers in brainstem = ↑ baroreceptor reflex

lateral tegmentum (NE pons-medulla tract)

regulate nociceptive input (analgesia) = descending path activates SC interneurons to INHIBIT pain input

NE LC tract roles

regulate arousal (via RAS activates alpha-2A), regulates memory, enhances cognitive performance, regulates reward, regulate mood

Tyramine

- tyr metabolite that acts as a false transmitter

- MAO inhibitors counter indicated: MOA-I = ↑ effect

- found in fermented foods, beer, cheese, sausage, red wine