More basic info/opinion wanted on opioid peptides and the BBB

Patrick Hurh HURH at FNAL.FNAL.GOV
Tue Feb 16 22:59:21 EST 1993


I've only got all you people to thank for propelling me on to a rudimentary
understanding of neurotransmitters and the like.... just for a stupid
sci-fi story!  But anyway...it is interesting and I'd like to get it right.
 Earlier I asked for endorphin references,    and got them!

Two books and a couple of articles later (I'm no longer a University
student so I have to wait on slow interlibrary loan to get my research
info), I feel a bit more educated but also confused/enticed/curious.  In
order to enable you to give me constructive advice on what I'm presently
writing, I'll have to reveal some of the plot of a short story which I have
already written but am not sure will 'work' technically.  Please don't make
a big deal out of the plot, I'm a sci-fi wannabe not a techno-god. 
Anyway...

In the not so distant future, a young woman finishes her graduate work in
neuroscience and is rejected by the new national health liscensing board
for physicians, not because she isn't qualified, but because she tested out
as an extremely good researcher on her national health exams.  Too many
qualified physicians were already filling the market and her test scores
implied a strong research potential.  This young woman is also a long
distance runner and often depends on her high level of beta-lipotropin
(beta-endorphin precursor) produced during states of stress (running) to
get her through frustrating lab work at a national pharmacological
conglomeration (physicians were nationalized, not pharmaceuticals). 
Eventually she discovers that the firm is covering up the fact that
endorphin/enkephalin precursors are readily manufactured by the average
human's extraneous glands (not just the pituitary) and is developing an
expensive synthesis technique so it can legitimately sell endorphins for a
_big_ profit.  The woman of the story decides to work within the system of
the pharmaceutical lab to reveal to the public that endorphins are created
in great quantities within the body, but never make it into the brain
_itself_ because of the BBB. In the mean time, she becomes addicted to her
own endorphins which she is extracting from her bloodstream immediately
after running and injecting into the pituitary area of the cerebral cortex
via a futuristic (no flames please) neural tap at the back of her neck
(originally installed to sample her neurotransmitter chemicals by the lab).
 Eventually this all boils to a head and a dismal conclusion is
drawn....but you'll have to read the story when it's finished.

As should be obvious from the above I am a little (a lot) confused about
the transport systems involved.  I have read a lot of stuff (_Endorphins,
New Waves In Brain Chemistry_ by Joel Davies) which make statements like ,
"They [L. Hawley and G. Butterfield of Univ. of Ca at Berkeley] note it's
an established fact that the opioid peptides are too large to pass through
the blood-brain barrier (BBB) and thus migrate from the bloodstream into
the brain."  Which supports my basic premise.  But also reports (articles)
like _Peptide Transport Systems for Opiates Across the Blood-Brain Barrier_
(Banks and Kastin, 1990) contend that transport is possible via saturable
and nonsaturable mechanisms.

However it seems that most of the studies propose that, while opiates are
readily transferred into the CNS, transfer into the brain itself is limited
especially for the larger precursors (ACTH and POMC).  In fact
beta-endorphin (which is proposed by Joel Davies in his book to be
resposible for at least some of runner's high (I'm aware of secondary
effects of 'satiated' CNS nerve cells)) was found not to transfer to the
interstitial fluids of the brain itself....

Can you kind, intelligent souls give me your opinion on, not only the
transfer of opioid peptides into the brain _itself_ (not only the CNS), but
also on the effect of introducing strong endorphins (beta-endorphin)
directly into the hippocampal area of the brain?  In the end of my story, I
have the main character altering her neural-tap to create a shunt (tunnel)
through the blood-brain barrier to let normally 'filtered' large endorphin
precursors created under stress directly into her brain where she thinks
(mistakenly) they will enhance her memory and intelligence (reminiscent of
vasopressin and met-enkephallins).

I know this probably a bit long of a request and a bit confusing, but I
would really like some technical input and opinions on whether my story
line (actually I've already written the story) holds any water.  Remember
it is is science-_fiction_ and the main implication is the impact of
neurophamacology on future society not the exact technical nature.   (but
as long as I use terms like endorphin and hippocampus, I'd like to have
some basis in reality)

BTW, the entire story was written as a hypertext entry to explain the term
'tunnel junkie' that I use in a longer novellette.  In other Words:  a
tunnel (shunt) through the blood-brain barrier is used in the future by
high-class drug addicts to allow direct injection of stress induced
(excercise/fright/amusement rides) endorphins into their brains for an
ultimate high.

Once again, please I consider this 'tunnel junkie' idea as copyright
material.  Please don't pass on the idea to friends who are writers, screen
artists etc... until I either (a) publish/release my stories or (b) an
appreciable time has passed (one year).

Thanks in advance,
                                        Patrick

HURH at FNAL.FNAL.GOV



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