Influence of estrogen and xenoestrogens on basolateral uptake of tetraethylammonium by opossum kidney cells in culture

Ryan M. Pelis, Randall C. Hartman, Stephen Wright, Theresa M. Wunz, Carlotta E. Groves

Research output: Contribution to journalArticle

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Abstract

The sex steroid hormone estrogen down-regulates renal organic cation (OC) transport in animals, and it may contribute to sex-related differences in xenobiotic accumulation and excretion. Also, the presence of various endocrine-disrupting chemicals, i.e., environmental chemicals that possess estrogenic activity (e.g., xenoestrogens) may down-regulate various transporters involved in renal accumulation and excretion of xenobiotics. The present study characterizes the mechanism by which long-term (6-day) incubation with physiological concentrations of 17β-estradiol (E2) or the xenoestrogens diethylstilbestrol (DES) and bisphenol A (BPA) regulates the basolateral membrane transport of the OC tetraethylammonium (TEA) in opossum kidney (OK) cell renal cultures. Both 17β-E2 and the xenoestrogen DES produced a dose- and time-dependent inhibition of basolateral TEA uptake in OK cell cultures, whereas the weakly estrogenic BPA had no effect on TEA uptake. Treatment for 6 days with either 1 nM 17β-E2 or DES reduced TEA uptake by ∼30 and 40%, respectively. These effects were blocked completely by the estrogen receptor antagonist ICI 182780 (Faslodex, fulvestrant), suggesting that these estrogens regulate OC transport through the estrogen receptor, which was detected (estrogen receptor α) in OK cell cultures by reverse transcription-polymerase chain reaction. The Jmax value for TEA uptake in 17β-E2- and DES-treated OK cell cultures was ∼40 to 50% lower than for ethanol-treated cultures, whereas Kt was unaffected. This reduction in transport capacity was correlated with a reduction in OC transporter OCT1 protein expression following treatment with both agents.

Original languageEnglish (US)
Pages (from-to)555-561
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume323
Issue number2
DOIs
StatePublished - Nov 2007

Fingerprint

Opossums
Tetraethylammonium
Estrogens
Diethylstilbestrol
Cell Culture Techniques
Kidney
Cations
Xenobiotics
Estrogen Receptors
Organic Cation Transporter 1
Down-Regulation
Endocrine Disruptors
Gonadal Steroid Hormones
Sex Characteristics
Reverse Transcription
Estradiol
Ethanol
Polymerase Chain Reaction
Membranes
fulvestrant

ASJC Scopus subject areas

  • Pharmacology

Cite this

Influence of estrogen and xenoestrogens on basolateral uptake of tetraethylammonium by opossum kidney cells in culture. / Pelis, Ryan M.; Hartman, Randall C.; Wright, Stephen; Wunz, Theresa M.; Groves, Carlotta E.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 323, No. 2, 11.2007, p. 555-561.

Research output: Contribution to journalArticle

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