Effect of cisplatin on the transepithelial potential difference of rat distal tubule.
Cisplatin, an effective anti-tumor agent, has significant effects on renal function including reduced glomerular filtration rate and potassium and magnesium wasting. It has been shown recently that cisplatin increases sodium conductance across the isolated frog skin, an effect which was inhibited by amiloride. The present study investigates the influence of cisplatin on the transepithelial potential difference (PD) of distal nephron segments of the rat kidney. Measurements were made under free-flow conditions and during distal microperfusion. When cisplatin was infused intravenously in a dose of 2 mg/kg/hr, the mean free-flow PD in late distal segments (cortical collecting tubules) increased from -18.5 +/- 1.4 mV (N = 37) to -31.2 +/- 1.4 mV (N = 36) (P less than 0.001). The large negative PD seen with cisplatin was abolished with intravenous amiloride, a mean PD of +0.9 +/- 1.5 mV (N = 22) (P less than 0.001) being obtained, similar to a PD of +1.9 +/- 1.5 mV (N = 39) found in control animals infused with amiloride. Perfusion of individual late distal segments with artificial plasma ultrafiltrate yielded a mean control PD of -12.4 +/- 1.2 mV (N = 21) and a significantly higher PD of -17.5 +/- 1.5 mV (N = 24) (P less than 0.01) when cisplatin (10(-3) M) was added to the perfusate. The addition of amiloride to these perfusates reduced the mean PDs to -3.2 +/- 0.5 mV (N = 19) and -3.6 +/- 0.7 mV (N = 17), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
G G
GG
Allen
L J
LJ
Barratt
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007473:Ion Channels / Q000187:drug effects*; D007684:Kidney Tubules / Q000187:drug effects*; D007686:Kidney Tubules, Distal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D051381:Rats; D011919:Rats, Inbred Strains
D007473:Ion Channels; D000584:Amiloride; D002945:Cisplatin