Effects of MK-196 and furosemide on rat medullary thick ascending limbs of Henle in vitro.
The effects of the diuretic agents, MK-196 (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy acetic acid) and furosemide on function of medullary thick ascending limb (tALH) isolated from the rat kidney were studied. tALH were dissected from whole kidneys of male Sprague-Dawley rats which were first perfused in vitro in a recirculating system for 10 to 15 min with a solution containing collagenase. Standard techniques for dissection and perfusion of tALH were followed. Control transepithelial voltage averaged +5.5 +/- 0.5 mV (n = 25). Drug concentration causing 50% inhibition of the voltage (EC50) was determined. EC50 for both MK-196 and furosemide in rat tALH was 8 X 10(-6) M (EC50 for MK-196 in rabbit tALH ws 7 X 10(-5) M). In other experiments, net chloride transport (JCl) in rat tALH averaged 142 +/- 19 pmol.mm-1.min-1 (n = 12), a value nearly twice that reported for the rabbit. In the rat, MK-196 (2 X 10(-4) M) reduced the voltage by 79 +/- 2% and JCl by 76 +/- 13% (n = 6). The same concentration of furosemide inhibited the voltage by 78 +/- 8% and the JCl by 104 +/- 4%(n = 5). Results indicate that: 1) rat tALHs dissected from collagenase-treated kidneys have functional characteristics similar to those reported for the rabbit tALH; and 2) the rat tALH is equally sensitive to MK-196 and furosemide, drugs which act to selectively inhibit active chloride transport.
D000818:Animals; D002712:Chlorides / Q000378:metabolism; D004232:Diuretics / Q000494:pharmacology*; D005665:Furosemide / Q000494:pharmacology*; D066298:In Vitro Techniques; D007189:Indans / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D007679:Kidney Medulla / Q000187:drug effects*; D007684:Kidney Tubules / Q000187:drug effects*; D008138:Loop of Henle / Q000187:drug effects*; D008297:Male; D003012:Microbial Collagenase / Q000494:pharmacology; D009399:Nephrons / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D002712:Chlorides; D004232:Diuretics; D007189:Indans; D007192:Indenes; D005665:Furosemide; C013352:indacrinone; D003012:Microbial Collagenase