Dear Jack,
You write;
At 01:03 PM 17-09-96 -0400, you wrote:
>Dear friends,>
>l Only
>the dopamine receptor cells in a structure in the basal ganglia were damaged,
>giving me a very atypical Parkinson's syndrome.
I am under the impression that dopamine producing cells are situated in the
basal ganglia, (latin for black substance)  Healthy dopamine producing cells
sendout branches to connect (synapse) with the D (dopamine) receptors in the
stiatum (latin for striped substance).  Initially it was thought there were
only 2 dopamine receptors, however it has been known for some time that
there are in fact 5.  At least 5 have now been identified, although the
function of D3 4, & 5, is not yet quite clear.  In the case of idiopathic
(cause unknown) P.D. as you know these cells gradually die of prematurely.
However it is thought that even when a diseased cell stops producing
dopamine from the levedopa precurser, it still has some storage capacity
left, which is why in the earlier stages of the disease these cells are
thought contribute to our ability to seem to make our medication last
longer.  Also there is thought that these diseased cells could be restored
to health given the right strimulus.  But I am getting of the point.  The
striatum consists of several bodies of cell mases, namely globus pallidus,
thalamus, putamen and some include part of the caudate nucleus.  When there
is an insufficient amount of dopamine produced in the basal ganglia it has
the effect of reducing the positive charge sent to the different parts of
the striatum.  This in turn produces a stronger negative response in the
chain and so on and so on.  So by destroying a small area in the appropriate
part of the brain the strength of the message or current is put hopefully
into balance.  This is of course an over simplification but I hope you see
what I mean.

>What I would like to know is this: Why would a typical P.D.er benefit from
>having the signals to the pallidus blocked, such as in a pallidotomy and/or a
>pallidal stimulation, when that brain structure is what controls the
>reception of dopamine, and injury to such would leave one in my condition.

I guess in your case, your brain is still producing dopamine in the correct
amount.  At least if no cells are damaged in the basal ganglia and your
problem is with the cells in the striatum.  In which  case your problem is
that you do not have enough receivers (receptors) to uptake the message or
stimulus from the basal ganglia.
The result is the same, as the signal is weakened resulting in to strong a
positive in the pallidus.

>I know that only a small and very specific part of the pallidus is actually
>frozen or de-activated by the two afore-mentioned procedures. However, the
>fact that P.D. can be caused by an over-active reception of dopamine
>confounds me. Maybe it has to do with there being less dopamine to receive,
>and the receptors are going haywire trying to receive dopamine that isn't
>there?

An over reactive, or over supply or stimulus of dopamine causes dyskinesia
(extra involuntary movement)  So if you take to much medication and the
receptors receive to much stimulus you get extra movement!  Early in P.D.
there are enough cells to uptake and store the dopamine, and release it when
needed as I said earlier.  When a healthy person takes levadopa orally they
do NOT get dyskinesia.  Only nausiated,   Because they have ample cells to
store the dopamine.  If what you say is correct, that your basal ganglia
cells are not damaged, than if my understanding of the situation is correct
you should not suffer from dyskinesia.  Do you?
Another school of thought is that when there is constantly an under supply
of dopamine being sent from the basal ganglia, the D receptors that are not
getting enough use eventually die.

>If somebody could help me out, it might add some understanding to all of our
>conditions.
>
>
I hope this explanation helps.  I purposely wrote this without going to my
text books so that I could explain it in simple English.  However I am only
a PWP who is trying to make sense of this disease so please correct me
any-body if I am technically incorrect.
Mary Thompson  48/6  [log in to unmask]