Glomerular effects of cholera toxin in isolated perfused rat kidney: A potential role for platelet activating factor

Cholera toxin (MW 84 kDa) is near considered a pharmacological tool to stud y the adenylyl cyclase system and a stimulus to generate platelet activatin g factor in the intestinal tract. We used this toxin to evaluate the renal haemodynamics, glomerular filtration function, tubular sodium transport and toxicity in isolated perfused rat kidney. Kidneys from adult male Wistar r ats were isolated for perfusion. The perfusion fluid was modified Krebs-Hen seleit solution and the samples were analyzed for sodium, potassium, inulin and osmolality. Clearance techniques were used to calculate physiological parameters. Cholera toxin (1.0 mu g/ml) caused a significant time-dependent reduction of glomerular filtration rate and urinary flow. This toxin also caused a small, but consistent reduction in fractional proximal sodium reab sortion (toxin = 67.43+/-2.42% versus control = 79.26+/-5.80%; P<0.025). WE B 2086, a platelet activating factor receptor antagonist at 100 mu g/ml com pletely blocked the effects induced by cholera toxin on glomerular filtrati on rate, fractional proximal sodium reabsortion and urinary flow. In contra st to cholera toxin, dibutyryl-cyclic AMP (10(-5) M) significantly increase d glomerular filtration rate (Db-cyclic AMP = 0.651+/-0.035 versus control = 0.514+/-0.043 ml.g(-1).min(-1).; P<0.025) in isolated perfused kidneys. D b-cyclic AMP caused a similar, but more severe reduction in fractional prox imal sodium reabsortion (Db-cyclic AMP = 54.21+/-2.35% versus control = 70. 10+/-3.24%; P<0.025). In addition Db-cyclic AMP increased significantly the urinary flow (Db-Cyclic AMP = 0.290+/-0.018 versus control = 0.179+/-0.026 ml.g(-1).min.(-1); P<0.025). WEB 2086+ Db-cyclic AMP also caused a signifi cant increase in the urinary flow with maximal effect at 90 min. (WEB+Db-cy clic AMP = 0.26+/-0.01 versus control = 0.15+/-0.01 ml.g(-1).min.(-1).; n = 8, P<0.025). Cholera toxin caused a decrease of urinary flow (toxin = 0.03 4+/-0.004 versus control = 0.145+/-0.02 ml.g(-1).min.(-1).; P<0.025), this effect was also completely abolished by WEB 2086 when it was injected previ ously to toxin. When only WEB 2086 was injected, the functional parameters remained stable throughout the perfusion time. Cholera toxin had no effect on renal vascular resistance, renal perfusate flow or tissue potassium, sug gesting renal integrity in kidneys treated with this toxin. The results sug gest that cholera toxin effects in the perfused rat kidney are primarily me diated by platelet activating factor.