RESUMEN
We have studied the effects of the diuretics mersalyl, furosemide and ethacrynic acid on renal gluconeogenesis is isolated rat-kidney tubules and on the activities of the most important gluconeogenic and glycolytic enzymes in both fed and fasted rats. Mersalyl (15 mg.kg-1 animal weight) significantly decreased the rate of gluconeogenesis in well-fed rats (68%) as well as in 24 and 48-h fasted ones (33 and 37% respectively). This inhibition occurred when lactate, pyruvate, glycerol or fructose were used as substrates. Ethacrynic acid at a dose of 50 mg.kg-1 animal weight provoked a transient inhibition of renal glucose production by almost 20% but only in fed rats with lactate as substrate, whereas the same dose of furosemide did not affect this metabolic pathway. Parallel to these changes, mersalyl caused a significant inhibition in the maximum activity of the most important gluconeogenic enzymes, phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase and glucose 6-phosphatase, in both fed and fasted rats. Neither ethacrynic acid nor furosemide produced any variations in the activities of these enzymes. The activity of the glycolytic enzymes phosphofructokinase and pyruvate kinase was not modified by these diuretics. Nevertheless, the activity of the thiol-enzyme glyceraldehyde 3-phosphate dehydrogenase was severely inhibited by mersalyl and to a lesser extent by the other diuretics. This inhibition was higher in fasted than fed rats. Hence, we conclude that the inhibitory effect of mersalyl on renal gluconeogenesis is due, at least partly, to a decrease in the flux through the gluconeogenic enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Ácido Etacrínico/farmacología , Furosemida/farmacología , Gluconeogénesis/efectos de los fármacos , Túbulos Renales/metabolismo , Mersalil/farmacología , Animales , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Ingestión de Alimentos , Ayuno , Fructosa-Bifosfatasa/metabolismo , Glucosa-6-Fosfato , Glucofosfatos/metabolismo , Gliceraldehído-3-Fosfato Deshidrogenasas/metabolismo , Técnicas In Vitro , Túbulos Renales/efectos de los fármacos , Hígado/efectos de los fármacos , Glucógeno Hepático/metabolismo , Masculino , Fosfoenolpiruvato Carboxiquinasa (GTP)/metabolismo , Fosfofructoquinasa-1/metabolismo , Piruvato Quinasa/metabolismo , Ratas , Ratas Wistar , Valores de ReferenciaRESUMEN
The effects of various lipogenic and antilipogenic states on the activities of rat-kidney cortex glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase have been studied. These conditions are related to the long-term administration of different diets, such as high-carbohydrate (80%) and high-fat (23%), and also to a state of fast. Contrary to what happens in liver cells and kidney cortex during a high protein diet administration, none of these nutritional conditions produced significant changes in the kinetics of either kidney hexose monophosphate dehydrogenases.