Presence of an endogenous factor in avian CNS with agonistic action on benzodiazepine receptors.
In the present paper we describe the presence in avian CNS of an endogenous inhibitor of [3H]flunitrazepam binding. This compound was extracted 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 C18 cartridges and several HPLC steps until an homogeneous peak was obtained. Its chemical structure was studied by size-exclusion chromatography of the purified material which indicated that it possesses a molecular weight below 1350. Although its inhibitory activity was lost by HCl treatment, its peptidic nature was ruled out by an amino acid and N-terminal sequence analyses. Ultraviolet absorption spectrum showed two main peaks at 230 and 280 nm. The endogenous compound was found to inhibit competitively [3H]flunitrazepam binding to its recognition site without affecting [3H]GABA binding to the same receptor complex. The behavior of the endogenous factor in an "in vitro" GABA "shift" test and GABA-dependent chloride flux experiments were similar to that of benzodiazepine receptor agonists. In conclusion, these results demonstrate the existence in avian CNS of a competitive endogenous inhibitor of benzodiazepine binding with agonistic action on benzodiazepine receptors.
Gravielle
M C
MC
Instituto de Biología Celular y Neurociencias Prof. E. De Robertis, Facultad de Medicina, Universìdad de Buenos Aires, Argentina.
Peña
C
C
Pignataro
L
L
Fiszer de Plazas
S
S
D000818:Animals; D002490:Central Nervous System / Q000502:physiology*; D002645:Chickens; D018118:Chloride Channels / Q000187:drug effects; D005445:Flunitrazepam / Q000378:metabolism; D018757:GABA Modulators / Q000378:metabolism; D058785:GABA-A Receptor Agonists; D016015:Logistic Models; D011869:Radioligand Assay
D018118:Chloride Channels; D018757:GABA Modulators; D058785:GABA-A Receptor Agonists; D005445:Flunitrazepam