EFFECTS OF VIBRIO-CHOLERAE ENTEROTOXIN PEPTIDE ON GLOMERULAR-FILTRATION RATE AND RENAL PROXIMAL TUBULAR SODIUM-TRANSPORT

Cholera toxin peptide stimulates adenylyl cyclase activity in several tissues and causes severe intestinal water and electrolyte secretion. To evaluate the regulatory function of sodium transport in renal tubul es, we studied the effect of cholera toxin peptide on rat kidneys. Iso lated kidneys from adult male hooded rats weighing 240-335 g were perf used with Krebs-Henseleit solution containing 60 mg/ml dialyzed bovine serum albumin (BSA). The effects of Vibrio cholerae peptide (CT; mole cular weight, approximately 82,000 Dalton) on glomerular filtration ra te (GFR), proximal sodium reabsorption (%pTNa+) and urinary flow rate (UF) were studied. All experiments were preceded by a 30-min control p eriod and in another group of kidneys the time course of the variables was followed without toxin infusion, for a paired control. Control ki dneys perfused with Krebs-Henseleit solution plus 60 mg/ml BSA present ed stable GFR (paired internal control GFR30 min = 0.596 +/- 0.248 ml g-1 min-1 vs GFR120 min = 0.694 +/- 0.362, N = 32; P > 0.05) and %pTNa + (%pTNa+30 min = 75 +/- 8.3 vs 84 +/- 1.6 for the internal control, N = 32; P > 0.05). CT caused a dose (0.03, 0.75 and 1.0 mug/ml)-depende nt decrease in GFR starting at 30 min and with a maximal peak of effec t at 90 min after toxin infusion (GFR(CT) = 0.130 +/- 0.086 ml g-1 min -1, N = 12, vs paired internal control GFR(Control/30 min) = 0.660 +/- 0.132, N = 12; P < 0.001). Additionally, CT (1.0 mug/ml) caused a sma ll decrease in %pTNa+ (%pTNa+ CT = 77 +/- 2.2, N = 12 vs paired intern al control %pTNa+Control/30 min = 84 +/- 1.6, N = 32; P = 0.003). The effect of CT (1.0 mug/ml) on the decrease in GFR was followed by a dro p in UF (UF(CT 90 min) = 0.027 +/- 0.003 ml g-1 min-1, N = 12, vs pair ed internal control UF(Control) = 0.093 +/- 0.002 ml g-1 min-1, N = 12 ; P<0.001). These results demonstrate that CT enterotoxin peptide prom otes a time- and dose-dependent decrease in GFR, UF and %pTNa+ in isol ated perfused kidneys.