Naslov
Organic anion transporters in the mammalian kidney

Autori
Sabolić, Ivan ; Ljubojević, Marija ; Herak-Kramberger, Carol-Mirna

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Book of Abstracts of the HDBMD 2004 / Dumić, Jerka - Zagreb : Hrvatsko društvo za biokemiju i molekularnu biologiju (HDBMB), 2004, 45-45

Skup
Congress of the Croatian Society of Biochemistry and Molecular Biology

Mjesto i datum
HOC Bjelolasica, Hrvatska, 30.09.2004. - 02.10.2004

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
gender differences; organic anions; membrane transporters

Sažetak
The kidneys play a crucial role in elimination of various endogenous and xenbiotic organic anions (OA). Proximal tubules (PT), with their specific transporters located in basolateral (BLM) and apical membranes of the epithelial cells, play the major role in this elimination. Previous studies of probenecid-sensitive p-aminohippurate (PAH) secretion indicated a multispecific transporter, represented by a tertiary active PAH/a-ketoglutarate exchange and localized in the PT cell BLM, as the pivotal mechanism for OA secretion in the nephron. Recently three multispecific OA transporters, OAT1, OAT2 and OAT3, which belong to a larger OAT family (SLC22A), have been cloned, characterized, and found to transport PAH and a variety of other substrates. Their mRNA's were detected in the kidney, and the relevant proteins were immunolocalized to BLM in the specific nephron segments. On the other side, OAT4, OAT5, and OAT8 were immunolocalizad either to the PT brush border membrane (OAT4 and OAT5) or to the specific membrane domains of the collecting duct cells (OAT8), suggesting their role in the exit step of OA secretion. Previous studies with rat kidney cortex slices in vitro indicated that the rate of renal OA transport is regulated by sex hormones, being a) greater in males (M) than females (F), b) diminished by castration of M, c) unaffected by ovariectomy of F, d) stimulated by treating gonadectomized rats with testosterone, and e) gender-independent in prepubertal rats. However, whereas a comparable expression pattern of the relevant mRNA's for OAT1 and OAT3 in the renal tissue was inconsistent, the immunolocalization studies clearly showed that the expression of OAT1 and OAT3 proteins in PT BLM was gender-dependent (M>F), upregulated by androgens, and downregulated by estrogens. At the luminal domain of the rat nephron, gender differences were found for OAT5 (F>M). These data indicate that gender differences in the rate of OA (PAH) secretion in the rat kidney are closely related to the abundance of OAT proteins in the respecitve membrane domains. The existence of gender differences and nephron segment- and cell-specific localizations of OAT's may be important for the kidney-related drug excretion, pharmacokinetics, and toxicity of anionic drugs.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA