Glutamate receptor agonist/antagonist and their metabolism

Christopheeee (spam free) "Hatton" at ifn-magdeburg.germany
Mon Sep 15 17:44:48 EST 1997


Hi all (message also sent to bionet.Neuroroscience and toxicology ngs.)

Having a bit of a wonder about some strange results we are getting from
an in vivo assay in Gerbils.  We anaethetize with sodium Pentobarbitol
and insert cannulae into hippocampus.  Then 8-9 days later add our
compounds.  

I realize this procedure will up regulate many enzyme systems, however
would this also include with the brain /blood-brain endothelium aswell. 
In particular I'm interested what if any Cyt. P450's etc would
metabolize these compounds,

(S)-4-Carboxy-3-phenylglycine  (or (s)-4C3HPG)
(R)-4C3HPG,

(R)-4-Carboxyphenylglycine and also its (S)-isomer

(RS)-3,5-Dihydroxyphenylglycine and its (S)-isomer

(S)- alpha-methyl-4-carboxyphenylglycine 

L-CCG-IV,  2S,3R,4S-2-(Carboxycyclopropyl)glycine and its 2S,3S,4S
stereoisomer

I ask because they have subtle effects on various Glutamte receptors,
and various isomers are more selective for subtypes.  If some of the
above are definatly being metabolized within the first few (1-8) hours,
it might explain our somewhat contradictory results.

I may be asking a lot, but I was thinking that after 8-9 days post
pentobarbitol most enzyme levels would return back to "pre-anaethesia
levels".  Secondly have I stumbled upon something as compounds are
injected icv into hippocampus.  Interesting i.p. injection of one of the
above gives different results to the icv injection suggeting first pass
metabolism or brain entry problems.  Also there is an "indication" that
those animals with
cannulae are more resistant to neuronal damage than i.p. controls.


Awaiting the combined wisdom of these 4 newsgroups because its beyond
this poor PhD students knowledge.


-- 
Christopher Hatton
Institute for Neurobiology
Dept. of Neurophysiology
PSF 1860
D-39008 Magdeburg
Germany
email: hatton at ifn-magdeburg.de
Tel.  (49) 0391-6263-432/402
Fax.  (49) 0391-6263-438



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