Mc. Gravielle et al., PRESENCE OF AN ENDOGENOUS FACTOR IN AVIAN CNS WITH AGONISTIC ACTION ON BENZODIAZEPINE RECEPTORS, Neurochemical research, 23(11), 1998, pp. 1395-1401
In the present paper we describe the presence in avian CNS of an endog
enous inhibitor of [H-3]flunitrazepam binding. This compound was extra
cted from a synaptic membrane fraction isolated from chick optic lobe
and brain using an exhaustive aqueous washing procedure, then purified
by means of solid-phase extraction with C-18 cartridges and several H
PLC steps until an homogeneous peak was obtained. Its chemical structu
re was studied by size-exclusion chromatography of the purified materi
al which indicated that it possesses a molecular weight below 1350. Al
though its inhibitory activity was lost by HCl treatment, its peptidic
nature was ruled out by an amino acid and N-terminal sequence analyse
s. Ultraviolet absorption spectrum showed two main peaks at 230 and 28
0 nm. The endogenous compound was found to inhibit competitively [H-3]
flunitrazepam binding to its recognition site without affecting [H-3]G
ABA binding to the same receptor complex. The behavior of the endogeno
us factor in an ''in vitro'' GABA ''shift'' test and GABA-dependent ch
loride flux experiments were similar to that of benzodiazepine recepto
r agonists. In conclusion, these results demonstrate the existence in
avian CNS of a competitive endogenous inhibitor of benzodiazepine bind
ing with agonistic action on benzodiazepine receptors.