Possible Interaction: Furosemide and Gamma-Aminobutyric Acid

“In human cerebellar receptors, only GABA antagonism by furosemide , but not the enhancement without added GABA, was observed.”

“ Furosemide specifically reverses the inhibition by gamma-aminobutyric acid ( GABA ) of t-[35S]-butylbicyclophosphorothionate ([35S]TBPS) binding and increases the basal [35S]TBPS binding to the cerebellar granule cell layer GABAA receptors.”

“These results indicate that, in pediatric epilepsy patients, increased GABA synaptic activity is associated with interictal FRs in the epileptogenic zone and suggest an active role of GABAergic interneurons in the generation of pathological HFOs.”

“However, in the presence of competitive GABA(A) receptor antagonists, the furosemide block of currents evoked by higher GABA concentrations was markedly increased.”

“In control, only currents evoked by low concentrations of GABA were significantly reduced in amplitude by furosemide , the alpha6 subunit-containing receptor antagonist.”

“The whole-cell currents induced by low concentrations of GABA (5 microM) or by the selective GABA(A)R agonist isoguvacine (7-25 microM) were enhanced by 200 microM furosemide.”

“… millimolar furosemide … GABA currents by 32.4+/-1.3% at -70 mV and by 76.7+/-5.0% at +70 mV. Analysis of the voltage dependence … GABA(A) channel pore with a dissociation constant of 5.3+/-0.5 mM at 0 mV and electric distance of 0.27.”

“The … furosemide of the … by GABA in alpha1alpha6beta2gamma2 [IC(50) = 298 +/- 116 microM (n = 7), assuming only one component] was not identical with inhibition of alpha6beta2gamma2 (IC(50) = … microM, n = 4), alpha1beta2gamma2 (IC(50) = 5,610 +/- 910 microM, n = 5), or a mixture of these components (assuming two components).”

“ Furosemide significantly inhibited the effect of GABA in ANT, but not in AT synaptosomes.”

“ Furosemide increases the basal tert-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding and reverses the inhibition of the binding by gamma-aminobutyric acid (GABA) in the cerebellar GABA(A) receptors containing the alpha6 and beta2/beta3 subunits.”

“ Furosemide , a loop diuretic and a specific antagonist of a cerebellar GABA(A) receptor population, and GABA decreased the inhibitory potencies of each other in the cerebellum, while enhanced them in the cortex.”