4.3 NOREPINEPHRINE AND THE ADRENERGIC RECEPTORS
4.3.1 The Adrenergic Neuronal System
Norepinephrine is another important neurotransmitter, and the receptors that respond to
norepinephrine and its analogs are referred to as adrenergicreceptors. The adrenergic
system, also sometimes known as the sympathetic nervous system, is found both periph-
erally (PNS) and centrally (CNS). Myelinated B-fibers originate in the spinal cord and
meet ganglion cells remote from the effector organ. Long, unmyelinated C-fibers then
transmit the impulse along the adrenergic axon from the ganglion to the synapses.
Peripherally,all organs are innervated sympathetically (as well as parasympatheti-
cally), and in most cases the adrenergic action of this system is opposite to the cholin-
ergic effects. The neurotransmitter secreted by the nerve endings is norepinephrine and,
to a lesser extent, epinephrine.
Centrally, two systems can be distinguished:
- The noradrenergic pathways, primarily situated in the locus ceruleus—a deeply
pigmented (hence the name, alluding to its blue color) small cell group involved in
behaviour, mood, and sleep. The cortex, some thalamic and hypothalamic centers,
and the cerebellar cortex are innervated from here. The noradrenergic pathways of
the tegmentum are less well known. - The adrenergic pathways that use epinephrine as a neurotransmitter, which have
been explored only recently. One of these systems is also tegmental and is mixed
with noradrenergic cells. The other is thalamic–hypothalamic, involved with the
vagus nerve. Some adrenergic fibers are also found in the fourth ventricle and the
spinal cord.
4.3.2 Adrenergic Neurotransmitter Metabolism
The adrenergic system produces neurotransmitters belonging to the chemical class
of substances known as catecholamines. These are derivatives of catechol (4.31,
o-dihydroxybenzene), with a β-aminoethyl side chain. The biogenetically related
catecholamines and the pathways leading to their biosynthesis are well-studied bio-
chemical pathways. Starting with tyrosine (4.32), the main pathway goes through dihy-
droxyphenylalanine (4.33) (DOPA), dopamine (4.34) (DA), norepinephrine (2.4) (NE,
also called noradrenaline in the European literature), and finally epinephrine(4.35)
(E, or adrenaline). The pathway is shown in figure 4.6.
While dopamine is an intermediate for NE and E, it is also a neurotransmitter in its
own right. Dopamine and the dopaminergic receptor, as well as drugs that act on it, are
discussed below.
4.3.2.1 Key Enzymes in Catecholamine Biosynthesis
The enzymes involved in catecholamine biosynthesis have been studied intensively
and are the targets of many drugs. The key enzyme is tyrosine hydroxylase, which
requires a tetrahydrofolate coenzyme, O 2 , and Fe^2 +, and is quite specific. As usual for
the first enzymes in a biosynthetic pathway, tyrosine hydroxylase is rate limiting, and
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