Effects of the diuretics furosemide,ethacrynic acid,and chlorothiazide on gluconeogenesis from various substrates in rat kidney cortex slices

Summary The effects of wide concentration ranges of furosemide, ethacrynic acid, and chlorothiazide on glucose formation by rat kidney cortex slices were investigated from fructose, pyruvate, lactate, and -ketoglutarate and partly at two different pH.Under control conditions without the drugs, more glucose was synthetized in moles/g dry weight · hour at the lower pH of 7.21 than at pH 7.49 without substrate as well as with the 5 substrates studied.Furosemide stimulated the rate of gluconeogenesis concentration dependent if fructose, pyruvate, or lactate were present as substrates. The percent increase was higher at pH 7.49 but the rates achieved with the maximal effective concentrations were about the same at both pH. The rate of glucose formation was only slightly enhanced from the substrates malate and -ketoglutarate. Ethacrynic acid enhanced the rate of glucose synthesis from fructose, pyruvate, and lactate, too, but had no stimulating effects, if malate or -ketoglutarate were the substrates. It exerted its effects at even lower concentrations than furosemide, but the maximal rates which could be observed were in the same range. Gluconeogenesis was not stimulated by chlorothiazide.Various and different sites of action on enzyme activities in the Embden-Meyerhof pathway are discussed for the two drugs influenced either directly by them or indirectly by changing concentrations of ATP or cyclic AMP.Preliminary reports of the results were presented in part at the joint meeting of the German and the Scandinavian Pharmacological Societies in Copenhagen 1971 and at the meeting of the Gesellschaft für Nephrologie in Aachen 1971.Supported by Deutsche Forschungsgemeinschaft Fu 45/4.