SYNTHESIS AND METABOLISM OF NORADRANALINE ::
The sympathetic transmission occurs in postganglionic sympathetic fibres and certain neurons of central nervous system Noradrenaline or norepinephrine is the transmitter at most of the sympathetic nerves in nigrostriatal tract the transmitter is dopamine Adrenaline or epinephrine is synthesized only in the adrenal medulla
The precursor for the synthesis of noradrenaline which is converted into tyrosine by the enzyme hydroxylase tyrosine is taken up by the adrenergic fibres where it is again hydrolyzed by the specific enzyme tyrosine hydroxylase into dihydroxy -phenylalanine (DOPA) This is the rate limiting step DOPA is decarboxylated by the enzyme DOPA decarboxylase to form dopamine This is taken up by the granules where it is converted into noradrenaline by dopamine B-hydroxylase in the adrenal medulla enzyme N-methyltransferase converts noradrenaline to adrenaline
Fig Sympathetic transmission
Noradrenaline synthesized in the adrenergic nerves gets bound to ATP molecule and is stored in the synaptic vessicles Upon stimulation of the nerve these synaptic vesicles move towards the membrane and get fused to Soon the membrane bursts opens and the transmitter is released This process of the release of noradrenaline is exocytosis The entire process from the stimulation of the nerve to the release of the transmitter is described as Excitation secretion coupling
Noradrenaline thus released acts on a-adrenoceptors to produce its effects Majority of its action is terminated by the uptake mechanism The act of noradrenaline being taken back from the synaptic cleft to the neurone is uptake or neuronal uptake from the neurone noradrenaline is also taken back into synaptic vesicles and is stored as usual This is granular uptake Besides neuronal and granular uptake the transmitter may be circulated and is taken up by other organs like spleen heart etc This is reffered to as uptake2 or Extraneuronal uptake
Metabolism of noradrenaline occurs by two enzymes ::
Catechol-o-methyl transferase (COMT) and monoamine oxidase (MAO) COMT is present outside the neurone whereas MAO is present within the neurone The major metabolite is 3-methoxy 4-hydroxymandelic acid
Effects of MAO and COMT on norepinephrine
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