Inhibition of P-glycoprotein transport: a mechanism for endocrine disruption in the channel catfish?
P-glycoprotein (pgp), an efflux transporter localized in a variety of tissues including the intestinal mucosa, renal tubules and bile canaliculi, is known to participate in the disposition of a variety of chemicals, including steroid hormones. This study examined the relationship of pgp to the movement into the bile of the hormone estradiol (E2), and the potential for transport interactions between the environmental pollutant nonylphenol ethoxylate (NPE) and E2. Biliary-cannulated in situ-prepared isolated perfused livers were used to assess pgp transport function. E2, in competitive transport preparations with Rhodamine 123 (Rho123), a pgp substrate, demonstrated significant decreases in Rho123 transport into bile, as did the prototypic inhibitor and substrate verapamil. [3H]E2 (0.28 nM) transport into bile was significantly reduced with either 20 M NPE or verapamil. These results suggest that E2 is a substrate and/or modulator for the catfish biliary pgp transporter, and that NPE potentially influences biliary transport and excretion of E2.
Kleinow
K M
KM
Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. kleinow@svac.vetmed.lsu.edu
Hummelke
G C
GC
Zhang
Y
Y
Uppu
P
P
Baillif
C
C
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001693:Biological Transport, Active / Q000187:drug effects; D002397:Catfishes / Q000378:metabolism*; D004958:Estradiol / Q000378:metabolism*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005026:Ethylene Glycols / Q000378:metabolism / Q000633:toxicity*; D008099:Liver / Q000378:metabolism; D020112:Rhodamine 123 / Q000378:metabolism; D014700:Verapamil / Q000378:metabolism / Q000494:pharmacology; D014874:Water Pollutants, Chemical / Q000378:metabolism / Q000633:toxicity*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D004965:Estrogen Antagonists; D005026:Ethylene Glycols; D014874:Water Pollutants, Chemical; D020112:Rhodamine 123; C021754:terics; D004958:Estradiol; D014700:Verapamil