R K Bhardwaj et al The Expression of OATPsOatps

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The tissue distribution of OATPs/Oatp isoforms has been extensively studied. Several isoforms demonstrate tissue-specific expression patterns of OATP-C (Konig et al., 2000a) and OATP-8 (Konig et al., 2000b), which are exclusively expressed at the basolateral membrane of the hepatocytes. In contrast, several OATP/Oatp family members (e.g., OATP-B, OATP-D, and OATP-E) have a fairly broad pattern of tissue expression including the blood-brain barrier (BBB), lung, heart, kidney, placenta, and intestine (Hagenbuch and Meier, 2003; Kim, 2003; van Montfoort et al., 2003).

Rat Oatp3 mRNA levels were similar down the length of the small intestine through the RNAse protection assay (Walters et al., 2000). Immunofluorescence studies further localized Oatp3 to the apical brush-border membrane of rat jejunal enterocytes (Walters et al., 2000) (Fig. 7.2). In contrast, expression of the human analogue OATP-A in the human small intestine has not been shown in the human small intestine (Tamai et al., 2000a), whereas evidence suggests the expression of OATP-B, OATP-D, and OATP-E isoforms, at least at the mRNA level (Tamai et al., 2000a). In a subsequent study, Kobayashi et al. (2003) identified the OATP-B isoform in the apical membrane of human intestinal epithelial cells by immuno-cytochemical analysis (Fig. 7.2). OATP/Oatp isoforms might play an important

Figure 7.2. Localization of intestinal drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), peptide transporter (PepTl), peptide histidine transporters (PHT1), monocarboxylate transporters (MCT), concentrative nucleoside transporter (CNT), equilibrative nucleoside transporter (ENT), organic anion transporting protein (OATP), multiple resistance protein (MRP) on the apical and basolateral membranes of the intestinal epithelial cells surrounding a hypothetical lumen

Figure 7.2. Localization of intestinal drug transporters P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), peptide transporter (PepTl), peptide histidine transporters (PHT1), monocarboxylate transporters (MCT), concentrative nucleoside transporter (CNT), equilibrative nucleoside transporter (ENT), organic anion transporting protein (OATP), multiple resistance protein (MRP) on the apical and basolateral membranes of the intestinal epithelial cells surrounding a hypothetical lumen

Basolateral Membrane

Basolateral Membrane role in the intestinal absorption of bile acids and other anionic drugs as well, considering that rat Oatp3 and human OATP-B mediate apical uptake of tauro-cholate, estrone-3-sulfate, and/or pravastatin in stably transfected cells (Walters et al., 2000; Kobayashi et al., 2003; Nozawa et al., 2004).

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