In vivo formation of benzodiazepine-like molecules in mammalian brain.
The possible cerebral formation of benzodiazepine (BDZ)-like molecules was evaluated in rats bilaterally microinjected into either the lateral ventricles (ICV) or the hippocampus (IH), with 10-70 microCi of different radiolabeled amino acids. After 3, or 24 h, the rats were sacrificed and BDZ-like molecules from total brain or hippocampus were purified by reversed phase HPLC. At 24 h. but not at 3 h of the ICV or IH microinjections with [3H] tryptophan, a peak of radioactivity containing material that inhibited the binding of [3H] flunitrazepam to both the BDZ receptor and the anti -BDZ monoclonal antibody MAb 21-7F9 was obtained. This active labeled fraction eluting just before diazepam also bound directly and specifically to the BDZ receptor and to MAb 21-7F9. No peak of radioactivity containing BDZ-like material was obtained when [3H] phenylalanine, [14C] glycine, [14C] methionine or [14C] tyrosine alone or in different combinations were microinjected into the hippocampus. The present results, together with our previous findings on the in vitro production of BDZ-like molecules in rat brain homogenates or slices (11), strongly suggest that the mammalian brain is capable of synthesizing low molecular weight substances possessing BDZ-like activity.
Instituto de Biologia Celular, Facultad de Medicina, Buenos Aires, Argentina.
J H
JH
Medina
M
M
Levi de Stein
C
C
Wolfman
C
C
Wasowski
A
A
De Blas
A C
AC
Paladini
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001569:Benzodiazepines / Q000302:isolation & purification / Q000378:metabolism*; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D001923:Brain Chemistry; D002250:Carbon Radioisotopes; D002552:Cerebral Ventricles / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005445:Flunitrazepam / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D011865:Radioisotope Dilution Technique; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D014316:Tritium
D000596:Amino Acids; D002250:Carbon Radioisotopes; D011963:Receptors, GABA-A; D014316:Tritium; D001569:Benzodiazepines; D005445:Flunitrazepam