Medical Pharmacology – Chapter 11 – Noradrenergic
neurotransmission
Noradrenaline functions as neurotransmitter in postganglionic
sympathetic neurons and in central noradrenergic neurons.
Biosynthesis and inactivation of noradrenaline
Biosynthesis;
Noradrenaline (NA) precursor is the amino acid L-tyrosine.
Tyrosine to DOPA is the rate-limiting step because TH activity is much
less than that of the other enzymes involved in the next conversion
steps in synthesis.
The DBH enzymes is located in granula (synaptic vescicles) so,
Dopamine has to be taken up in synaptic vesicle before it can be
converted into NA
In dopaminergic neurons (found in CNS) there is no DBH enzyme. It is
present in the chromaffin cells of the adrenal medulla. Most of these
cells also contain phenylethylamine-N-methyltransferase (PNMT) that
converts NA into adrenaline.
Inactivation;
Inactive NA is taken up in noradrenergic nerve ending and re-
stored in granula
NA also absorbed by other cells (e.g. glia cells) and inactivated
enzymatically.
Inactivation of NA by enzymes;
Monoamine-oxidase (MAO); present in mitochondria of
both neuronal and non-neuronal cells and in blood plasma.
Break down amines (adrenaline, noradrenaline). NA
become 3,4-dihydroxymandelic acid.
Provides most contribution to the enzymatic inactivation,
because largely located in nerve endings
Catechol-O-methyltransferase (COMT); present in most tissues, especially
kidneys and liver. Inactivation of catecholamine
neurotransmitters (dopamine, adrenaline and noradrenaline) by
introducing a methyl group to the catecholamines. NA become
nor metadrenaline
Provides less contribution to the enzymatic inactivation,
because less located in nerve endings
Most important NA metabolite which is more or less a reflection of
sympathetic activity is VMA, found in high concentration in urine.
Inhibitors of MAO and COMT are used to treat Parkison’s disease.
Adrenoreceptors Pharmacological control of noradrenergic
neurotransmission
neurotransmission
Noradrenaline functions as neurotransmitter in postganglionic
sympathetic neurons and in central noradrenergic neurons.
Biosynthesis and inactivation of noradrenaline
Biosynthesis;
Noradrenaline (NA) precursor is the amino acid L-tyrosine.
Tyrosine to DOPA is the rate-limiting step because TH activity is much
less than that of the other enzymes involved in the next conversion
steps in synthesis.
The DBH enzymes is located in granula (synaptic vescicles) so,
Dopamine has to be taken up in synaptic vesicle before it can be
converted into NA
In dopaminergic neurons (found in CNS) there is no DBH enzyme. It is
present in the chromaffin cells of the adrenal medulla. Most of these
cells also contain phenylethylamine-N-methyltransferase (PNMT) that
converts NA into adrenaline.
Inactivation;
Inactive NA is taken up in noradrenergic nerve ending and re-
stored in granula
NA also absorbed by other cells (e.g. glia cells) and inactivated
enzymatically.
Inactivation of NA by enzymes;
Monoamine-oxidase (MAO); present in mitochondria of
both neuronal and non-neuronal cells and in blood plasma.
Break down amines (adrenaline, noradrenaline). NA
become 3,4-dihydroxymandelic acid.
Provides most contribution to the enzymatic inactivation,
because largely located in nerve endings
Catechol-O-methyltransferase (COMT); present in most tissues, especially
kidneys and liver. Inactivation of catecholamine
neurotransmitters (dopamine, adrenaline and noradrenaline) by
introducing a methyl group to the catecholamines. NA become
nor metadrenaline
Provides less contribution to the enzymatic inactivation,
because less located in nerve endings
Most important NA metabolite which is more or less a reflection of
sympathetic activity is VMA, found in high concentration in urine.
Inhibitors of MAO and COMT are used to treat Parkison’s disease.
Adrenoreceptors Pharmacological control of noradrenergic
neurotransmission
