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

Douglas Fitts dfitts at carson.u.washington.edu
Thu Feb 18 20:56:51 EST 1993


HURH at FNAL.FNAL.GOV (Patrick Hurh) writes:


[...plot of sci-fi story omitted...]


>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

What?  CNS is brain and spinal cord.  What do you mean "brain itself"
as distinct from CNS?

>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

Here it is again?  Are you just excluding cord?  

You should try looking up circumventricular organs.  These are small 
nuclei in the brain that lack a blood-brain barrier.  They are
specialized for detecting hormones in the blood and passing information
about the concentrations of these hormones to other areas inside the
BBB.  This is the main reason your gimmick won't work:  the CVO's  
would detect any hormone with the kind of biological importance of
the kind you describe. CVOs include the subfornical organ, area
postrema, organum vasculosum laminae terminalis, median eminence, 
and so on.  They are all midline structures located on the wall
of the third and fourth ventricles.  One of them, the subcommissural
organ, curiously has an intact BBB (too bad -- it's close to the dentate
gyrus of the hippocampus).  These structures contain receptors for
just about every peptide anybody has bothered to look for, including
opiates. 
 
>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).

No clue, sorry.

[omitted rest of article]

>Thanks in advance,
>                                        Patrick

>HURH at FNAL.FNAL.GOV

Best wishes on your story.

Doug
dfitts at u.washington.edu



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