Adrenalin/epinephrine

Adrenalin/epinephrine

• Adrenalin/epinephrine

• Serotonin

• GABA

• Histamine

• Dopa & dopamine

• thyroxin

L-dopa

• L-dopa

• Dopamine

• Noradrenalin or Norepinephrine

• Adrenalin or epinephrine

Family members act as neurotransmitters in the brain and hormones in the circulatory system

• Family members act as neurotransmitters in the brain and hormones in the circulatory system

• Produced in adrenal medulla and sympathetic neurons

• The pools are kept separate by the blood brain barrier

The flight or fight response

• The flight or fight response

• Adrenalin and noradrenalin are produced in the adrenal medulla and stored in granules

• Released into the circulation by stimuli from the sympathetic nervous system

• They bind to specific receptors

Glycoproteins which span the membrane

• Glycoproteins which span the membrane

• Known as G-coupled protein receptors

• 4 classes of adrenergic receptors: 1, 2, 1, 2

• Some are stimulatory (β) some inhibitory (α)

• Activate or inhibit adenylyl cyclase  cAMP

Have short term and long term effects

• Have short term and long term effects

• The alpha receptors stimulate smooth muscle contraction in peripheral organs

• the beta receptors mobilise fuels, relax smooth muscles of the bronchi and blood vessels supplying skeletal muscles and increase heart rate.

The end result of these actions is to mobilise and shunt energy reserves to where they are most needed

• The end result of these actions is to mobilise and shunt energy reserves to where they are most needed

• prepare for action!

• Treatment for cardiac arrest and anaphylactic reactions

• Bronchodilator properties used in asthma

• Agonists and antagonists to adrenergic receptors are also used as drugs

Noradrenalin is uniquely found between the junctions of sympathetic neurons and smooth muscle cells

• Noradrenalin is uniquely found between the junctions of sympathetic neurons and smooth muscle cells

• Decreased levels of noradrenalin in the brain are associated with some forms of clinical depression

Strategies to increase noradrenalin levels in the brain:

• Strategies to increase noradrenalin levels in the brain:

• Inhibit inactivation (monoamine oxidase inhibitors or MAO inhibitors)

• OR

• Inhibit reuptake (tricyclics)

L-dopa and dopamine

• L-dopa and dopamine

• Dopamine is also a neurotransmitter in synapses in localised areas of the brain stem

• Parkinson’s disease is caused from the degeneration of these dopaminergic neurons.

• The psychotic symptoms of Schizophrenia are associated with elevated dopamine

Parkinson patients are treated with L-dopa or levadopa

• Parkinson patients are treated with L-dopa or levadopa

• Although it is dopamine that is deficient it cannot cross the blood brain barrier

• L-dopa crosses the barrier (on amino acid transporters), where it is decarboxylated to produce dopamine

• It is usually administered with a peripheral decarboxylase inhibitor; carbidopa (to prevent the L-Dopa going to dopamine before it gets to the brain).

The rate limiting step in the pathway

• The rate limiting step in the pathway

• Adding another –OH to the aromatic ring

• It requires O2 and biopterin (this moiety also makes up folates – we obtain it from our diet or microorganisms in the gut)

• This is a tricky reaction

• There are only a few examples of this in life!

Although it is the rate limiting step in synthesis it is not a great site for drug action.

• Although it is the rate limiting step in synthesis it is not a great site for drug action.

• There are drugs that inhibit the enzyme but these are rarely used

• Regulation of adrenalin is done at the release phase

• Most drugs work on the receptor

There are 3 isoforms produced by alternative splicing although the biological significance of these is not entirely clear.

• There are 3 isoforms produced by alternative splicing although the biological significance of these is not entirely clear.

• Another example of a similar reaction is the conversion of phenylalanine to tyrosine

• The enzyme here is phenylalanine hydroxylase

• This reaction also requires biopterin

The conversion of phenylalanine to tyrosine is a similar hydroxylation

• The conversion of phenylalanine to tyrosine is a similar hydroxylation

• Catalysed by phenylalanine hydroxylase

• If this enzyme is defective the phenylalanine has to go elsewhere

• Accumulates as phenylpyruvate

thyroxin levels too low; individuals present with lethargy, cold skin and often overweight.

• thyroxin levels too low; individuals present with lethargy, cold skin and often overweight.

• low iodine in the diet often the result of low iodine in the soil….leads to a goiter

Thyroxin is essential for normal growth and development

• Thyroxin is essential for normal growth and development

• A deficiency will result in cretinism, a condition defined by mental retardation, stunted growth

A derivative synthesised by the decarboxylation of tryptophan.

• A derivative synthesised by the decarboxylation of tryptophan.

• A neurotransmitter

• low levels of serotonin have also been linked to depression.

• Prozac acts to inhibit the degradation of serotonin.

Produced by the decarboxylation of histidine

• Produced by the decarboxylation of histidine

• A common product of allergic reactions, produced by mast cells

• Neurotransmitter

• Involved in sleep regulation

• Regulates acid secretions in the stomach

• Antihistamines are used to relieve the symptoms of an allergic reaction

Gamma amino butyric acid

• Gamma amino butyric acid

• Produced by the decarboxylation of glutamate

• Major inhibitory neurotransmitter

• Released by 30% of synapses

Adrenalin/epinephrine

• Adrenalin/epinephrine

• Serotonin

• GABA

• Histamine

• Dopa & dopamine

• thyroxin