Dissociation of [35S]t‐Butylbicyclophosphorothionate Binding Differentiates Convulsant and Depressant Drugs that Modulate GABAergic Transmission

G. Maksay, M. K. Ticku

Resultado de la investigación: Articlerevisión exhaustiva

77 Citas (Scopus)

Resumen

Abstract: The dissociation of [35S]t‐butylbicyclophosphorothionate ([35S]TBPT) from binding sites on membranes from rat cerebral cortex, after addition of saturating concentrations of convulsant and depressant drugs, was studied. The addition of unlabeled TBPT, picrotoxinin, or pentamethylenetetrazol resulted in dissociation patterns that were monophasic and not distinguishable, suggesting that these convulsants bind competitively to the same (convulsant) sites. In contrast, γ‐aminobutyric acid (GABA) greatly facilitated [35S]TBPT dissociation by binding allosterically to the GABA recognition site of the receptor‐ionophore complex. TBPT dissociation was similarly accelerated by the depressants etazolate, (+)‐etomidate, and barbiturates. The convulsant and depressant S(+) and R(‐) stereoisomers of N‐methyl‐5‐phenyl‐5‐propyl‐barbituric acid displayed large stereoselectivity in the acceleration of TBPT dissociation. These results suggest that depressants bind to sites different from the convulsant sites of the allosteric GABA receptor complex, or the binding of depressants to the same population of sites elicits negative cooperativity and dissociates the convulsants.

Idioma originalEnglish (US)
Páginas (desde-hasta)480-486
Número de páginas7
PublicaciónJournal of neurochemistry
Volumen44
N.º2
DOI
EstadoPublished - feb. 1985
Publicado de forma externa

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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