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Information About The Catecholamines





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The Catecholamines
- The Happy Family of Neurotransmitters


Possibly the 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 sympathetic stuff.

They found 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 norepinephrine?"

Then it was noted that yet another chemical, dopamine, had the same catechol and amino group as epinephrine and noradrenaline.

At which 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!

And indeed they are.

A Happy Family of Neurotransmitters

In the 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 not?

Well, 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 hydroxylase.

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.

Cells that make norepinephrine and epinephrine also produce these two enzymes. But they don't release dopamine. Instead, it is quickly converted by another enzyme, dopamine-beta-carboxylase, into norepinephrine. Neurons that have all three enzymes are norepinephrinergic neurons (zounds! what a mouthful).

In the 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?).

Four enzymes and some tyrosine and you have a whole family of neurotransmitters.

Certainly there must be agonist and antagonists for the family.

Catecholamine Receptor Agonists and Antagonists

Let's do dopamine first. Dopamine does have several different receptor types. They are called D1, D2, D3, etc. receptors.

Really! 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:

  1. 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.
  2. 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 schizophrenia.

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 sympatheticomimetic drugs. 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.

There are 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.

Got it?

Degradation of Catecholamines

Like 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.

Source: Northeastern University, Physical Therapy Dept.; 6 Robinson Hall; 360 Huntington Ave.; Boston, MA 02115



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