Possible involvement of organic anion and cation transporters in renal excretion of xanthine derivatives, 3-methylxanthine and enprofylline.
Whether organic anion and cation transporters are involved in the renal excretion of xanthine derivatives, 3-methylxanthie and enprofylline, remains unclear. In this study, we have investigated the effects of typically predominant substrates for organic anion and cation transporters on the tubular secretion of 3-methylxanthine and enprofylline in rats. In the renal clearance experiments using typical substrates for organic anion transporters, probenecid and p-aminohippurate, probenecid (20 mg/kg), but not p-aminohippurate (100 mg/kg), significantly decreased the renal clearance and clearance ratio of 3-methylxanthine and enprofylline. The typical substrates for organic cation transport systems, tetraethylammonium (30.6 mg/kg) and cimetidine (50 or 100 mg/kg), significantly decreased the renal clearance and clearance ratio of 3-methylxanthine and enprofylline. These results suggest that the renal secretory transport of 3-methylxanthine and enprofylline are mediated by probenecid-, cimetidine- and tetraethylammonium-sensitive transport systems. Uric acid, an organic anion, significantly inhibited the renal secretion of 3-methylxanthine, but not enprofylline, suggesting that the renal tubular transport of 3-methylxanthine is also mediated via uric acid-sensitive transport system. These findings suggest the possibility that both organic anion and cation transporters are, at least, involved in the renal tubular transport of 3-methylxanthine and enprofylline in rats.
Nadai
Masayuki
M
Faculty of Pharmacy, Meijo University, 150 Yagotoyama, Tenpaku-ku, Nagoya, 468-8503, Japan.
Kato
Miki
M
Yoshizumi
Hideo
H
Kimura
Masao
M
Kurono
Shunsuke
S
Abe
Fumie
F
Saito
Hiroko
H
Hasegawa
Takaaki
T
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007684:Kidney Tubules / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D027361:Organic Anion Transporters / Q000096:biosynthesis / Q000502:physiology*; D027701:Organic Cation Transport Proteins / Q000096:biosynthesis / Q000502:physiology*; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity; D019789:Tetraethylammonium / Q000494:pharmacology; D013997:Time Factors; D014970:Xanthines / Q000493:pharmacokinetics* / Q000652:urine; D010130:p-Aminohippuric Acid / Q000494:pharmacology
D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D014970:Xanthines; D019789:Tetraethylammonium; D002927:Cimetidine; C034347:enprofylline; D011339:Probenecid; C029703:3-methylxanthine; D010130:p-Aminohippuric Acid