RESUMO
Isatin (2,3-dioxoindole) competitively inhibited (27-40%) Na(+)-dependent L-lysine uptake in rat intestine. The value of Kt was increased from 3.04 mM in control to 5.88 mM in presence of 10 mM isatin. Effect of isatin on the Na(+)-independent amino acid uptake was insignificant (12-18%). The inhibitory constant (Ki) was 2.8 mM under these conditions. The observed inhibition was unaffected by -SH group reacting agents. Isatin (1-10 mM) inhibited Na+, K(+)-ATPase activity in intestine in vitro, the maximum inhibition (66%) being at 10 mM isatin concentration. But the drug had no effect on enzyme activity under in vivo conditions.
Assuntos
Mucosa Intestinal/metabolismo , Isatina/farmacologia , Lisina/metabolismo , Animais , Transporte Biológico/efeitos dos fármacos , Cinética , Ratos , Sódio/farmacologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/metabolismo , Reagentes de Sulfidrila/farmacologiaRESUMO
10 mM isatin (2,3-dioxoindole) inhibited glucose influx into human erythrocytes by over 30%. The inhibition is of the competitive type, where the affinity constant (Kt) was increased from 5.71 (control) to 11.11 mM in the presence of isatin with no change in Vmax (130 nmol/min/ml packed cells). The observed inhibition of sugar transport by isatin was not mediated through membrane -SH groups accessible to iodoacetate, iodoacetamide, DTNB, DNP or sodium arsenite. Isatin inhibited sugar transport in the presence of 2 mM harmaline, an alkaloid inhibitor of Na+, K(+)-ATPase activity. The inhibition was non additive which suggests that these two compounds interact with the same or a similar site on the erythrocyte membrane.
Assuntos
Glicemia/metabolismo , Eritrócitos/metabolismo , Isatina/farmacologia , Arsenitos/farmacologia , Transporte Biológico/efeitos dos fármacos , Dinitrofenóis/farmacologia , Ácido Ditionitrobenzoico/farmacologia , Interações Medicamentosas , Eritrócitos/efeitos dos fármacos , Harmalina/farmacologia , Humanos , Iodoacetamida/farmacologia , Iodoacetatos/farmacologia , Ácido Iodoacético , Cinética , Compostos de Sódio/farmacologia , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , TermodinâmicaRESUMO
Isatin (10 mM) inhibited the activity of rabbit brush border sucrase by 60% at pH 5.0 but it had no effect on enzyme activity around neutral pH. Isatin inhibition of sucrase was unaffected by Na+ ions but K+ and Cs+ ions reduced enzyme inhibition, partially. Kinetic analysis revealed that sucrase inhibition by isatin at acidic pH was non-competitive with Ki of the order 6.5-7.8 mM. Isatin together with 4 mM harmaline or iodoacetate (3 mM) or dithionitrobenzene (2 mM) yielded 80-85% inhibition of the enzyme. These observations suggest that inhibitory sites for isatin, harmaline and -SH group reacting agents are distinct in rabbit brush border sucrase.
