second neurotransmitter to be discovered
was initially called sympathetic because
it was produced by stimulation of the
sympathetic nerves, and it had the
opposite effect of acetylcholine on the
heart. And like vagusstuf, the name
sympathetin was discarded as soon as the
chemists got their hands on the
that it contained a chemical group
called a catechol group
and an amino group, and
were probably all ready to call this
neurotransmitter catecholamine when
someone, probably an physiologist, noted
that the adrenal glands also produced a
different chemical called
adrenaline that had the same
catechol and amino group. So sympathetin
couldn't be called catecholamine since
there was another. How about
noradrenaline? "Wait a minute!"
called out an American scientist. "In
the good old U.S.A, we call adrenaline
epinephrine. That way
our ER doctors can say, 'Quick! Inject
10 ccs of epi right into the heart.
Stat!'. So why not call the chemical
was noted that yet another chemical,
dopamine, had the same
catechol and amino group as epinephrine
point the chemist decided that he didn't
care what the physiologists called these
neurotransmitters. Each chemical had
both a catechol group and an amino
group. They were all catecholamine!
indeed they are.
Family of Neurotransmitters
beginning there was tyrosine, a common
amino acid. All cells are loaded with
tyrosine. But all cells, and all
neurons, do not make dopamine,
norepinephrine and epinephrine. All
cells are not catecholaminergic
(thank heavens, what a mouthful). Why
it's in the genes. All cells do not
express the genes necessary for the
production of the enzymes needed to
synthesize the catecholamine
neurotransmitters. As you should recall
from our discussion of acetylcholine,
it's enzymes that determine which
neurotransmitter is produced. If a
neuron makes ChAT, the cell will produce
acetylcholine and be a cholinergic
neuron. In the case of the
catecholamines, the enzymes are a bit
more complicated, but let's see if we
can figure it out. All cells contain
tyrosine, but only catecholaminergic
cells contain the enzyme tyrosine
Tyrosine hydroxylase coverts
tyrosine into a chemical that is almost
the neurotransmitter dopamine. The
chemical is called L-dopa.
It takes a second enzyme, a
amino acid decarboxylase, to
finish the job. All dopaminergic
neurons have both of these enzymes and
can therefore make dopamine.
that make norepinephrine and epinephrine
also produce these two enzymes. But they
don't release dopamine. Instead, it is
quickly converted by another enzyme,
Neurons that have all three enzymes are
neurons (zounds! what a mouthful).
CNS and PNS that's the end of story, but
to be complete, the adrenal glands have
these three enzymes and another, let's
just call it enzyme number 4, which
converts the norepinephrine into
epinephrine before it is released. Thus,
the adrenal gland cells are...
adrenergic (okay, you could say
epinephrinergic. But why?).
enzymes and some tyrosine and you have a
whole family of neurotransmitters.
there must be agonist and antagonists
for the family.
Catecholamine Receptor Agonists and
dopamine first. Dopamine does have
several different receptor types. They
are called D1, D2, D3, etc. receptors.
Sounds like chemists named them to me.
And while there are many drugs that act
as dopamine agonists and antagonists,
all I'd like for you to know is that:
L-dopa is the precursor for
dopamine. It is used to treat
diseases like Parkinson's disease
because, unlike dopamine, L-dopa
crosses the blood brain barrier.
Giving L-Dopa to Parkinson's disease
patients works as long as neurons
with amino acid decarboxylase are
still functioning in the brain. They
convert the L-Dopa into dopamine.
Dopamine antagonists and often
called dopamine blockers. There are
D1 blockers and D2 blockers, etc.
These are useful in the treatment of
diseases with too much like
Huntington's chorea. And
Norepinephrine has many agonists, but
the one you should know is ...
epinephrine. For the most part
norepinephrine and epinephrine have the
same receptors. Thus each is an agonist
for the other. And here's my favorite
term, drugs that are agonists for these
receptors are called
Because these drugs turn on the
sympathetic nervous system just like
norepinephrine and epinephrine. When the
heart stops, just yell, "10 ccs of a
sympatheticomimetic. Stat!" and look at
all the confused faces.
two different main types of receptors
for these neurotransmitters, called
alpha and beta receptors. The difference
is in the antagonists. Let's keep this
simple. Alpha blockers block alpha
adrenergic receptors and beta blockers
antagonize beta adrenergic receptors.
Degradation of Catecholamines
acetylcholine, degradation enzymes help
to terminate the action of the
neurotransmitter. There are two main
enzymes which I will merely list without
getting into the details -- monoamine
oxidase (MAO), and catechol-O-methyl
transferase (COMT). Of these, MAO
inhibiting drugs are very important in
increasing dopamine levels in
Parkinson's disease patients.
Northeastern University, Physical
Therapy Dept.; 6 Robinson Hall; 360
Huntington Ave.; Boston, MA 02115