Effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), an adenosine A1-receptor antagonist, on urinary excretions of various electrolytes in rats.
We examined the effects of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), an adenosine A1-receptor antagonist, on urine volume and urinary excretions of various electrolytes in saline-loaded rats, as compared with those of furosemide, trichlormethiazide (TCM), acetazolamide and amiloride. KW-3902 at doses of 0.001-1 mg/kg (p.o.) significantly increased urine volume and excretions of sodium, calcium, magnesium, chloride and bicarbonate. In addition, KW-3902 shifted urine pH to alkaline and decreased free water reabsorption. KW-3902 did not induce kaliuresis, whereas furosemide (30 mg/kg, p.o.), TCM (1 mg/kg, p.o.) and acetazolamide (25 mg/kg, p.o.) induced kaliuresis. In the KW-3902-treated group, the increases in bicarbonate excretion and urine pH were less prominent than those induced by acetazolamide, and the excretions of sodium, calcium, magnesium and chloride were similar to those induced by furosemide. The present results suggest that the adenosine A1-receptor antagonist exhibits diuresis by the inhibited reabsorption of electrolytes, not only at the proximal tubule but also at the distal tubule.
Nagashima
K
K
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Karasawa
A
A
D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D004573:Electrolytes / Q000378:metabolism* / Q000652:urine; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009994:Osmolar Concentration; D058915:Purinergic P1 Receptor Antagonists; D051381:Rats; D017208:Rats, Wistar; D014970:Xanthines / Q000494:pharmacology*
D004232:Diuretics; D004573:Electrolytes; D058915:Purinergic P1 Receptor Antagonists; D014970:Xanthines; C073525:rolofylline