Renal tubular site of action of KW-3902, a novel adenosine A1-receptor antagonist, in anesthetized rats.
The mechanism of the diuretic action of KW-3902 (8-(noradamantan-3-yl)-1,3-dipropylxanthine), an adenosine A1-receptor antagonist, was investigated by a lithium clearance study and stop-flow method in anesthetized rats. KW-3902 increased urine volume (UV), sodium excretion and renal clearances of sodium (CNa) and lithium (CLi), when UV and CNa increased more than CLi. KW-3902 did not affect the stop-flow pattern, whereas trichlormethiazide inhibited the reabsorption of water and sodium at the distal nephron. These results suggest that the adenosine A1-receptor blockade exhibits diuretic effects via the inhibition of reabsorption of water and sodium mainly at the proximal tubule. The additional small contribution of the distal action can not be ruled out.
Mizumoto
H
H
Department of Pharmacology, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
Karasawa
A
A
D000818:Animals; D004232:Diuretics / Q000494:pharmacology*; D007684:Kidney Tubules / Q000187:drug effects*; D008094:Lithium; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D058914:Purinergic Antagonists; D051381:Rats; D017208:Rats, Wistar; D014970:Xanthines / Q000494:pharmacology*
D004232:Diuretics; D058914:Purinergic Antagonists; D014970:Xanthines; C073525:rolofylline; D008094:Lithium