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Adrenalin

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Adrenalin

Adrenaline (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

  • Heart rate increase
  • Increase in blood pressure due to vasoconstriction
  • Bronchiolar dilation
  • Fast energy supply through
    • Fat reduction (lipolysis)
    • Release and biosynthesis of glucose
    • Insulin inhibition
    • Increased glucose uptake in muscles
  • Centralization of blood circulation
  • Inhibition of gastrointestinal activity
  • Sweat production
  • Goose bumps (pilomotor reflex)
  • Pupil dilation (mydriasis)
  • Dry mouth
  • Regulation of blood clotting
  • Regulation of fibrinolysis
  • Stress hormone
    • Participation in fight-or-flight response

2. Formation of adrenaline

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

Dopamine is produced in several steps:

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

This remains the case in dopaminergic cells.
In noradrenergic cells:

  • Dopamine is synthesized by the enzyme
  • Dopamine β-hydroxylase (DHB) with consumption of oxidized vitamin C
  • To noradrenaline

This remains the case in noradrenergic cells.
In adrenergic cells:

  • Noradrenaline is produced by the enzyme
  • Phenylethanolamine N-methyltransferase (PNMTase) with consumption of 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 into adenosine and homocysteine by the enzyme S-adenosylhomocysteine.
Homocysteine can be remethylated to methionine or broken down to the amino acid cysteine.

Feedback path:

Increased adrenaline inhibits the formation of L-tyrosine and thus also the synthesis of dopamine and noradrenaline.

The regular adrenaline 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. Reduction of adrenaline

Adrenaline is broken down 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, adrenaline has a half-life of 1 to 3 minutes.2

4. Adrenaline receptors

Adrenaline binds with the same affinity to

  • Α1-adrenoceptor
    • Increases central blood volume
      • Due to contraction of small blood vessels
      • Especially in the skin and kidneys
    • Contraction of the smooth muscles
      • Contraction of the urinary bladder sphincter muscle
  • Α2-adrenoceptor
    • Mobilization of energy reserves

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

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

      • After pre-treatment with alpha-blockers
      • Due to very low adrenaline doses (< 0.1 µg/kg)
    • Relaxation of the smooth muscles

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

      • Increase in blood sugar levels due to the release and formation of new glucose
      • Release of glucagon
  • Β2-adrenoceptor
    • Dilation of central and muscle-supplying blood vessels
    • Mobilization of energy reserves
      • Increase in energy turnover
  • Β3-adrenoceptor
    • Mobilization of energy reserves
      • Lipolysis through activation of hormone-sensitive lipase
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