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Adrenalin

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Adrenalin

Adrenaline (English: epinephrine) is a monoamine and catecholamine. It acts as a hormone in the body and as a neurotransmitter in the brain. Adrenaline cannot cross a healthy blood-brain barrier.

1. Effect of adrenaline

Adrenaline in the blood conveyed

  • Heart rate increase
  • Blood pressure increase due to blood vessel constriction
  • Bronchioles dilation
  • Fast energy supply due to
    • Fat loss (lipolysis)
    • Release and biosynthesis of glucose
    • Insulin Inhibition
    • Increased glucose uptake in muscles
  • Centralization of blood flow
  • Inhibition of gastrointestinal activity
  • Sweat production
  • Goose bumps (pilomotor reflex)
  • Dilation of the pupil (mydriasis)
  • Dry mouth
  • Regulation of blood clotting
  • Regulation of fibrinolysis
  • Stress hormone
    • Involvement in fight-or-flight response

2. Adrenaline formation

Adrenaline is formed from noradrenaline, which in turn is formed from dopamine.1

Dopamine is produced in several steps:

  • L-phenylalanine from food.
  • Is produced by phenylalanine hydroxylase with consumption of tetrahydrobiopterin, folic acid and oxygen
  • To L-tyrosine
  • This is achieved by tyrosine hydroxylase consuming calcium citrate
  • To L-Dopa (dihydrixyphenylalanine)
  • This is achieved by dopa decarbxylase consuming vitamin B6 (pyridoxal phosphate)
  • To dopamine (3,4-dihydroxyphenyethanolamine) and CO2 (carbon dioxide)

In dopaminergic cells, it remains so.
In noradrenergic cells:

  • Dopamine is produced by the enzyme
  • Dopamine-β-hydroxylase (DHB) under consumption of oxidized vitamin C
  • To norepinephrine

In noradrenergic cells, this remains the case.
In adrenergic cells:

  • Norepinephrine is produced by the enzyme
  • Phenylethanolamine N-methyltransferase (PNMTase) consuming S-adenosylmethionine (SAM), pyridoxal phosphate and vitamin B12
  • To adrenaline.

SAM is formed from a reaction of the amino acid methionine with ATP (adenosine triphosphate).
SAM is converted to adenosine and homocysteine by the enzyme S-adenosylhomocysteine.
Homocysteine can be remethylated back to methionine or degraded to the amino acid cysteine.

Feedback path:

Increased adrenaline inhibits L-tyrosine formation and, at the same time, dopamine and noradrenaline synthesis.

The regular epinephrine blood level is less than 100 ng/l (about 500 pmol/l).

In the brain, adrenaline is produced in cells of the area reticularis superficialis ventrolateralis. There it probably supports the regulation of blood pressure.

3. Adrenaline degradation

Epinephrine is degraded by COMT to metanephrine and further by MAO-A to vanillinmandelic acid and 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG), which are excreted in the urine.
At normal COMT levels, epinephrine has a half-life of 1 to 3 minutes.2

4. Adrenaline receptors

Adrenaline binds with equal affinity to

  • Α1-adrenoceptor
    • Increases central blood volume
      • By contraction of small blood vessels
      • Especially in skin and kidneys
    • Smooth muscle contraction
      • Contraction of the sphincter of the urinary bladder
  • Α2-adrenoceptor
    • Energy reserve mobilization

      • Inhibition of insulin β1-adrenoceptor productions
    • Increased heart rate (positive chronotropic)

      • Accelerated excitation conduction (positive dromotropic)
      • Increased contractility (positive inotropic)
      • Lowering of the stimulus threshold (positive bathmotropic)
    • Paradoxical lowering of blood pressure (adrenaline reversal)
      probably by selective activation of β2-adrenoceptors of blood vessels

      • After pretreatment with alpha-blockers
      • By very low doses of adrenalin (< 0.1 µg/kg)
    • Smooth muscle slackening

      • Immobilization of the gastrointestinal tract (peristalsis inhibition)
      • Dilatation of the bronchi
      • Relaxation of the uterus in pregnant women
    • Mobilization of energy reserves

      • Increase in blood glucose level due to release and reformation of glucose
      • Glucagon release
  • Β2-adrenoceptor
    • Dilatation of central and muscle-supplying blood vessels
    • Mobilization of energy reserves
      • Increase of the energy turnover
  • Β3-adrenoceptor
    • Mobilization of energy reserves
      • Lipolysis by activation of hormone-sensitive lipase
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