Probenecid potentiates the hyperglycaemic effect but reduces the diuretic effect of frusemide in mice

Abstract

1 The effect of probenecid on frusemide-induced diuresis and hyperglycaemia was studied in mice. 2 Probenecid, a known inhibitor of tubular secretion of organic anions in the kidney, strongly reduced the diuretic response to frusemide (25 or 200 mg kg-' body weight). This effect of probenecid appeared to be dose-dependent up to 240 mg kg-' body weight, at least at the lower concentration of frusemide. 3 Pretreatment with probenecid (240 mg kg-' body weight) potentiated the hyperglycaemic effect of frusemide (25 or 200 mg kg-' body weight). 4 The results show that probenecid has opposite effects on frusemide-induced diuresis and hyperglycaemia in mice. It is suggested that the acute hyperglycaemic effect of frusemide is not directly linked to diuresis.

Furosemide Treatment Causes Age‐Dependent Glucose Intolerance and Islet Damage in Obese‐Hyperglycaemic Mice

“…In order to elucidate the mechanisms behind the diabetogenic effect of the loop diuretic furosemide, we have previously studied its effect on the carbohydrate metabolism in adult lean as well as obese-hyperglycaemic mice (ob/obmice) (Sandstrom 1987;Sandstrom & Sehlin 1988a & b). We found that a single injection of furosemide (200 mg/kg body weight) induced acute hyperglycaemia in both mouse strains but that long-term glucose intolerance developed only in ob/ob-mice (Sandstrom 1987;Sandstrom & Sehlin 1988a & b). This made in tempting to speculate that the inheritance of the ob/ob genome, as such, is linked to the susceptibility to develop disturbed carbohydrate metabolism after furosemide treatment.…”

“…Furosemide causes disturbed carbohydrate metabolism also in laboratory animals (Foy 1967;Wales et a/. 1968;Aynsley-Green & Alberti 1973;Foy & Furman 1971, 1972Sandstrom 1987;Sandstrom & Sehlin 1988a &. b).…”

The influence of co‐administered organic acids on the kinetics and dynamics of frusemide.

“…The ability of probenecid to completely block the natriuretic and diuretic actions of frusemide in the dog has never been demonstrated in man (Chennavasin et al, 1979;Homeida et al, 1977;Honari et al, 1977). Further examples of inter-species differences are that probenecid blocks the diuresis induced by frusemide, but not by bumetanide, in the cat (Friedman & Roche-Ramel, 1977), and in mice probenecid appears to cause dose-dependent reductions in frusemide-induced diuresis (Sandstrom, 1986). In man probenecid decreases the renal clearance of frusemide by a third (present study) to a half (Chennavasin et al, 1979).…”