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

The effect of probenecid on frusemide-induced diuresis and hyperglycaemia was studied in mice. 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-1 body weight). This effect of probenecid appeared to be dose-dependent up to 240 mg kg-1 body weight, at least at the lower concentration of frusemide. Pretreatment with probenecid (240 mg kg-1 body weight) potentiated the hyperglycaemic effect of frusemide (25 or 200 mg kg-1 body weight). 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.