Wednesday, April 14, 2004

Explain This, Intelligent Design Hypothesizers!!!

Brain-targeted drug offers impotence hope
from Nature (subscription required)

Rat results hint at possible alternative to Viagra.
14 April 2004


A new brain drug gives erections to lab rats - raising the possibility that it could some day rival existing human sexual dysfunction therapies such as Viagra.

The new molecule, called ABT-724, is a variant of an anti-impotence drug called apomorphine, which is currently on offer to European men. Both work by activating receptors in the brain for a molecule called dopamine, triggering a rush of blood to the penis.

But whereas apomorphine stimulates all dopamine receptors, ABT-724 targets only a subset of these, called D4 receptors, report researchers led by Jorge Brioni of Abbott Laboratories in Abbott Park, Illinois. This could potentially sidestep the side-effects, such as nausea and vomiting, suffered by some apomorphine users. [...]

Information is transmitted in the brain by various small molecules known as neurotransmitters.  These are, essentially, chemical messengers that carry information from one nerve cell to the other.  The message is received when the neurotransmitter binds to a site on the nerve cell.  These binding sites are called receptors.  There are dozens of neurotransmitters, and each can act on a number of different receptors.  Dopamine is a neurotransmitter in the catecholamine family.  For dopamine, there are at least five families of receptors, labeled D1 through D5. 

The human D4 receptor has a peculiar history.  In 1992, it was discovered that the D4 receptor has multiple genetic variants.  It was the first such receptor that was known to have this kind of diversity.  It was found that there were at least three different kinds of D4, each coded for by a different allele.  That means that not every person makes the D4 receptor in exactly the same way. 

This was a milestone in the evolution of our understanding of the human brain.  It turns out that for ever layer of complexity we discover, there is another layer beneath.  To use dopamine as an example, the first testable biological model of schizophrenia was called the dopamine hypothesis.  The idea was that an excess of dopamine was the cause of schizophrenia.  This led to the finding that dopamine receptors are located in specific areas of the brain, each area serving a different function.  Then it was learned that there are different families of dopamine receptors.  Then it was learned that, within each family, there are several variations.  As this was being worked out, it was learned that nerve cells somehow can change the number of receptors present, and can subtly alter how sensitive the receptors are to the transmitter.  No doubt, the story is even more complicated than this.  Although it has been established firmly that dopamine is involved in the pathophysiology of schizophrenia, we still do not know what the root of the problem is.  However, by working with the dopamine hypothesis, several drugs have been developed that modify dopamine signaling.  This has helped innumerable people lead better lives.  But not all dopamine-modulating drugs are used for their effects on the brain.

Apomorphine, the drug used by our European cousins to enhance their erectile functioning, turns on dopamine receptors.  This includes the D4 receptor, which is why it helps with erections.  However, it has an unfortunate adverse effect.  You see, some dopamine receptors are given the task of detecting possible poisons that could be absorbed by our intestines and get into the bloodstream.  There is a spot in the brain called the chemoreceptor trigger zone.  The CTZ is full of dopamine receptors.  When chemicals float by in the bloodstream, the CTZ tries to tell if the chemicals are bad.  If so, it triggers the vomiting center. 

Now we learn that the D4 receptor has an unexpected role.  It is involved in the male of the species having erections.  Here we see that nature found a way to have the brain control sexual functioning.  That seems intelligent, right?  After all, we can't have humans running around having erections without some kind of executive control.  That would lead to all kinds of immoral behavior.  So, nature intelligently provided us with a way to exercise some self-control, by building a linkage between the thinking side of us, and what you might call the carnal side.  But nature has a way of playing little tricks.  The same chemical that causes erections also causes vomiting.  Now, is this intelligent design? 

God, in his wisdom, made the fly
And then forgot to tell us why.
--Ogden Nash

God in her  wisdom, created D4
And then forgot to tell us what for.
---Corpus Callosum