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Tissue distribution and phenobarbital induction of target SLC‐ and ABC ‐ transporters in cattle
Author(s) -
Zancanella V.,
Giantin M.,
Lopparelli R. M.,
Nebbia C.,
Dacasto M.
Publication year - 2013
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/j.1365-2885.2012.01427.x
Subject(s) - atp binding cassette transporter , transporter , efflux , biology , phenobarbital , pharmacology , multidrug resistance associated protein 2 , gene , gene expression , microbiology and biotechnology , genetics
In veterinary pharmaco‐toxicological sciences, few data about uptake and efflux drug transporters (DTs) expression and regulation phenomena have been published. In this study, the tissue distribution and transcriptional modulation of solute carrier ( SLC ) and ATP ‐binding cassette ( ABC ) DT s were investigated in cattle orally administered with phenobarbital ( PB ) by using a quantitative real‐time RT ‐ PCR approach. The criterion for target gene selection was the PB ‐responsiveness in human and rodent model species. All target DTs were expressed in the liver. Only two of the seven PB ‐responsive target DT s ( SLCO 1 B 3 and SLC 10 A 1) were not constitutively expressed in cattle extra‐hepatic tissues. The greatest number of DT s ( SLCO 2 B 1, ABCB 1, ABCC 2, ABCG 2) were expressed in intestine and testis, followed by, adrenal gland ( SLCO 2 B 1, ABCB 1, ABCG 2), lung ( ABCB 1, ABCG 2), kidney, and skeletal muscle ( ABCG 2). PB administration never altered DT s m RNA levels, except for an increase in hepatic ABCC 2 m RNA and a down‐regulation of renal ABCG 2. Altogether, these results confirm only to some extent data obtained in humans and laboratory species; clearly, they should be considered a preliminary step for further molecular investigations about species‐differences in DT gene expression and regulation as well as in DT expression and function.