Effect of a novel diuretic, 7-chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(IH)-quinolinone-4-oxime-o- sulfonic acid, potassium salt (M17055) on Na+ and K+ transport in the distal nephron segments.
By using an in vitro microperfusion technique, we examined whether a novel loop diuretic, 7-Chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(IH)-quinolinone-4-oxime-o-sul fonic acid, potassium salt (M17055), a derivative of quinolinone oxime sulfonic acids, affects Na+ and K+ transport in the distal nephron segments, including the cortical collecting duct and connecting tubule (CNT) isolated from rabbit kidneys. M17055 added to the lumen at 1 mM caused a positive deflection of transepithelial voltage (VT) by 2.2 +/- 0.4 mV. The response was less than that evoked by 10 microM amiloride (8.9 +/- 0.1 mV). In the collecting duct cell of the cortical collecting duct from normal rabbits, M17055 depolarized the basolateral membrane by 9.2 +/- 1.3 mV, whereas amiloride hyperpolarized it by 7.6 +/- 2.4 mV. In the cortical collecting duct from deoxycorticosterone acetate-treated rabbits, despite the fact that both agents depolarized the basolateral membrane of the collecting duct cell, amiloride consistently hyperpolarized the apical membrane, whereas M17055 did not cause any significant changes in apical membrane voltage. In the presence of 2mM Ba++ in the lumen, the apical membrane voltage deflection by M17055 was abolished. In addition, the magnitude of the apical membrane voltage deflection caused by an abrupt increase in luminal K+ concentration from 5 to 50 mM was significantly reduced. In the CNT, both amiloride and M17055 caused a positive deflection of VT. However, M17055 depolarized the basolateral membrane by 6.6 +/- 1.6 mV, whereas amiloride hyperpolarized it by 4.4 +/- 1.1 mV.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Jichi Medical School, Tochigi.
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Yasoshima
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Yamasaki
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T
Shinkawa
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K
Yoshitomi
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Imai
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D003900:Desoxycorticosterone / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology*; D066298:In Vitro Techniques; D007685:Kidney Tubules, Collecting / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009399:Nephrons / Q000187:drug effects* / Q000378:metabolism*; D010091:Oximes / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism / Q000493:pharmacokinetics*; D015221:Potassium Channels / Q000187:drug effects; D015363:Quinolones / Q000494:pharmacology*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism / Q000493:pharmacokinetics*; D015222:Sodium Channels / Q000187:drug effects
D004232:Diuretics; D010091:Oximes; D015221:Potassium Channels; D015363:Quinolones; D015222:Sodium Channels; D001464:Barium; C079648:7-chloro-2,3-dihydro-1-(2-methylbenzoyl)-4(1H)-quinolinone 4-oxime-O-sulfonic acid; D003900:Desoxycorticosterone; D000584:Amiloride; D012964:Sodium; D011188:Potassium