Details of a Researcher - ITAGAKI Shiro

Papers - ITAGAKI Shiro

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Effects of sex hormones on regulation of ABCG2 expression in the placental cell line BeWo.

S Yasuda, S Itagaki, T Hirano, K Iseki

JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES ( CANADIAN SOC PHARMACEUTICAL SCIENCES ) 9 ( 1 ) 133 - 139 2006.01 [Refereed]

PURPOSE: The aim of this study was to elucidate the effects of sex hormones that are secreted during gestation from the placenta on ABCG2 mRNA and protein expression levels by using the placental cell line BeWo. METHODS: We investigated the effects of estrogens ( estrone, 17-beta-estradiol and estriol) on the expression level of ABCG2 mRNA by RT-PCR. The expression level of ABCG2 protein was analyzed by Western blot analysis. We also investigated the localization of ABCG2 in BeWo cells by Western blot analysis of the plasma membrane fraction and by immunohistochemistry. RESULTS: It was found that all estrogens induce the expression of ABCG2 mRNA in a concentration-dependent manner. Furthermore, Western blot analysis showed that 17-beta-estradiol induces the expression of ABCG2 protein. Western blot analysis of the plasma membrane fraction and immunohistochemistry showed that ABCG2 localized on only the apical side of BeWo cells and that 17-beta-estradiol had no effect on the localization of ABCG2. In addition, progesterone suppressed the induction of ABCG2 expression by 17-beta-estradiol at 1-10 mu M. CONCLUSION: The expression of ABCG2 in the placenta is regulated by estrogen and progesterone during gestation.

PubMed

Cloning and functional identification of slc5a12 as a sodium-coupled low-affinity transporter for monocarboxylates (SMCT2)

Srinivas, SR, E Gopal, L Zhuang, S Itagaki, PM Martin, YJ Fei, Ganapathy, V, PD Prasad

BIOCHEMICAL JOURNAL ( PORTLAND PRESS LTD ) 392 655 - 664 2005.12 [Refereed]

We report in the present paper, on the isolation and functional characterization of slc5a12, the twelfth member of the SLC5 gene family, from mouse kidney. The slc5a12 cDNA codes for a protein of 619 amino acids. Heterologous expression of slc5a12 cDNA in mammalian cells induces Na+-dependent transport of lactate and nicotinate. Several other short-chain monocarboxylates compete with nicotinate for the cDNA-induced transport process. Expression of slc5a12 in Xenopus oocytes induces electrogenic and Na+-dependent transport of lactate, nicotinate, propionate and butyrate. The substrate specificity of slc5a12 is similar to that of slc5a8, an Na+-coupled transporter for monocarboxylates. However, the substrate affinities of s1c5a12 were much lower than those of slc5a8. slc5a12 mRNA is expressed in kidney, small intestine and skeletal muscle. In situ hybridization with sagittal sections of mouse kidney showed predominant expression of slc5a12 in the outer cortex. This is in contrast with slc5a8, which is expressed in the cortex as well as in the medulla. The physiological function of slc5a12 in the kidney is likely to mediate the reabsorption of lactate. In the intestinal tract, slc5a 12 is expressed in the proximal parts, whereas slc5a8 is expressed in the distal parts. The expression of slc5a12 in the proximal parts of the intestinal tract, where there is minimal bacterial colonization, suggests that the physiological function of slc5a12 is not to mediate the absorption of short-chain monocarboxylates derived from bacterial fermentation but rather to mediate the absorption of diet-derived short-chain monocarboxylates. Based on the functional and structural similarities between slc5a8 and slc5a12, we suggest that the two transporters be designated as SMCT1 (sodium-coupled monocarboxylate transporter 1) and SMCT2 respectively.

DOI PubMed

Transepithelial transport of telmisartan in Caco-2 monolayers

Y Goto, S Itagaki, S Umeda, M Kobayashi, T Hirano, K Iseki, K Tadano

BIOLOGICAL & PHARMACEUTICAL BULLETIN ( PHARMACEUTICAL SOC JAPAN ) 28 ( 12 ) 2235 - 2239 2005.12 [Refereed]

Telmisartan is the most recently marketed angiotensin 11 type I receptor antagonist. Drug-drug interactions involving transporters can directly affect the therapeutic safety and efficacy of many important drugs. In clinical practice, telmisartan is coadministered with many kinds of drugs. However, little is known about the contribution of transporters to the intestinal transport of telmisartan. The aim of this study was to determine the transport mechanism of telmisartan across intestinal epithelial cells. In the presence of an inwardly directed proton gradient, the apical-to-basal transport of telmisartan was greater than basal-to-apical transport. Thus, we focused on the uptake mechanism of telmisartan across brush-border membranes. The uptake of telmisartan by Caco-2 cells was shown to be energy- and proton-dependent. Although some monocarboxylates inhibited the uptake of telmisartan, L-lactic acid, which is a typical substrate of the monocarboxylate transporter (MCT) 1-MCT4, did nor affect the uptake of telmisartan. Preloading of acetic acid enhanced the uptake of telmisartan, showing a trans-stimulation effect. These results suggest that the carrier-mediated transport system is involved in the uptake of telmisartan by Caco-2 cells and that the apical-localized transport system is similar to MCTs, but not MCT1-MCT4. It is possible that telmisartan reduce the absorption of coadministered drugs by sharing the MCTs. Since MCTs have an important role in the intestinal absorption of pharmacologically active compounds, it is important to be aware of the potential of telmisartan-drug interactions involving MCTs and to act in order to prevent undesirable and harmful consequences.

DOI CiNii

Expression level of ABCG2 in the placenta decreases from the mid stage to the end of gestation

S Yasuda, S Itagaki, T Hirano, K Iseki

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY ( TAYLOR & FRANCIS LTD ) 69 ( 10 ) 1871 - 1876 2005.10 [Refereed]

The aim of this study was to elucidate the expression pattern of ABCG2 in the placenta from the mid stage to the end of gestation. rABCG2 expression was investigated in rats on the 14th gestation day (gd) and the 20th gd. Expression of the rABCG2 gene and expression of rABCG2 protein in the placenta were detected on gd 14 by RT-PCR and Western blot analysis respectively. The expression level of rABCG2 on gd 20 was less than that on gd 14. We investigated whether progesterone, secreted from the placenta, regulates the expression of ABCG2 in BeWo cells. Expression levels of the ABCG2 gene and protein in BeWo cells were decreased by progesterone treatment. We conclude that progesterone plays a role in reduction in the expression level of ABCG2 in the placenta with the advance of gestation from the mid stage to the end of gestation.

DOI PubMed CiNii

Phenolsulfonphthalein transport by potential-sensitive urate transport system

S Itagaki, S Shimamoto, M Sugawara, M Kobayashi, K Miyazaki, T Hirano, K Iseki

EUROPEAN JOURNAL OF PHARMACOLOGY ( ELSEVIER SCIENCE BV ) 518 ( 2-3 ) 83 - 89 2005.08 [Refereed]

The purpose of this study was to elucidate the transporter-mediated secretion systems for phenolsulfonphthalein in brush-border membranes. In human and rat renal brush-border membranes, a potential-sensitive transport system has been shown to be involved in the efflux of organic anions. The uptake of phenolsulfonphthalein into rat renal brush-border membrane vesicles was stimulated by an inside-positive membrane potential. This potential-sensitive uptake of phenolsulfonphthalein was inhibited by probenecid, pyrazinoate and urate. p-Aminohippurate had no effect on the potential-sensitive uptake of phenolsulfonphthalein. Moreover, urate competitively inhibited the uptake of phenolsulfonphthalein. On the other hand, the uptake of phenolsulfonphthalein was slightly increased in the presence of an outward Cl- gradient. These results suggest that phenolsulfonphthalein has high affinity for the potential-sensitive urate transport system but has low affinity for an anion exchanger. (c) 2005 Elsevier B.V. All rights reserved.

DOI PubMed

Nateglinide uptake by a ceftibuten transporter in the rat kidney brush-border membrane.

Kobayashi M, Saito Y, Itagaki S, Hirano T, Iseki K

Biochimica et biophysica acta ( 1 ) 1715 ( 1 ) 19 - 24 2005.08 [Refereed] [International journal]

Nateglinide, a novel oral hypoglycemic agent, possesses a carbonyl group and a peptide-type bond in its structure. We previously reported that nateglinide transport occurs via a single system that may be identical to the ceftibuten/H(+) cotransport system by the rat small intestine. We speculated that the absorption system present on the intestinal epithelium may be similar to that found on the renal tubular epithelium. The aim of this study was to characterize the transporters on the apical side of the kidney that may contribute to the reabsorption of ceftibuten and nateglinide. The uptake of nateglinide by rat renal brush-border membranes is associated with an H(+)-coupled transport system. Ceftibuten competitively inhibited H(+)-dependent nateglinide uptake. In contrast, Gly-Sar, cephradine and cephalexin had no effect on nateglinide uptake. Nateglinide competitively inhibited H(+)-driven transporter-mediated ceftibuten uptake. We conclude that nateglinide transport occurs via a single system that is H(+)-dependent and may be identical to the ceftibuten/H(+) cotransport system.

DOI PubMed

Nateglinide uptake by a ceftibuten transporter in the rat kidney brush-border membrane

M Kobayashi, Y Saito, S Itagaki, T Hirano, K Iseki

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES ( ELSEVIER SCIENCE BV ) 1715 ( 1 ) 19 - 24 2005.08 [Refereed]

Nateglinide, a novel oral hypoglycemic agent, possesses a carbonyl group and a peptide-type bond in its structure. We previously reported that nateglinide transport occurs via a single system that may be identical to the ceftibuten/H+ cotransport system by the rat small intestine. We speculated that the absorption system present on the intestinal epithelium may be similar to that found on the renal tubular epithelium. The aim of this study was to characterize the transporters on the apical side of the kidney that may contribute to the reabsorption of ceftibuten and nateglinide. The uptake of nateglinide by rat renal brush-border membranes is associated with an H+-coupled transport system. Ceftibuten competitively inhibited H+-dependent nateglinide uptake. In contrast, Gly-Sar, cephradine and cephalexin had no effect on nateglinide uptake. Nateglinide competitively inhibited H+-driven transporter-mediated ceftibuten uptake. We conclude that nateglinide transport occurs via a single system that is H+-dependent and may be identical to the ceftibuten/H+ cotransport system. (c) 2005 Elsevier B.V. All rights reserved.

DOI

Substrate specificity of the nateglinide/H+ cotransport system for phenolic acids

Y Saito, S Itagaki, Y Otsuka, Y Kobayashi, H Okumura, M Kobayashi, T Hirano, K Iseki

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ( AMER CHEMICAL SOC ) 53 ( 15 ) 6100 - 6104 2005.07 [Refereed]

In clinical, patients usually take many kinds of drugs at the same time. Thus, drug-drug interactions involving transporters can often directly affect the therapeutic safety and efficacy of many important drugs. However, there have been few studies on food-drug interactions involving transporters. Dietary polyphenols have been widely assumed to be beneficial for human health. Polyphenols are found ubiquitously, and they are commercially prepared and used as functional foods. We have reported that ferulic acid, which is one of the most well-known polyphenols and is used as a functional food, affected the transport of nateglinide, an antidiabetic drug, by Caco-2 cells. In this study, we investigated the effects of other polyphenols on the nateglinide/H+ transport system. We report here that caffeic acid and p-coumaric acid have a different inhibitory manner on the uptake of nateglinide. The results of this study are useful to identify the substrate specificity of the nateglinide/H+ cotransporter.

DOI PubMed CiNii

Transport mechanism for L-lactic acid in human myocytes using human prototypic embryonal rhabdomyosarcoma cell line (RD cells)

M Kobayashi, Fujita, I, S Itagaki, T Hirano, K Iseki

BIOLOGICAL & PHARMACEUTICAL BULLETIN ( PHARMACEUTICAL SOC JAPAN ) 28 ( 7 ) 1197 - 1201 2005.07 [Refereed]

Monocarboxylate transporter (MCT), which cotransport L-lactic acid and protons across cell membranes, are important for regulation of muscle pH. However, it has not been demonstrated in detail whether MCT isoform contribute to the transport Of L-lactic acid in skeletal muscle. The aim of this study was to characterize L-lactic acid transport using an human rhabdomyosarcoma (RD) cell line as a model of human skeletal muscle. mRNAs of MCT 1, 2 and 4 were found to be expressed in RD cells. The [C-14] L-lactic acid uptake was concentration-dependent with a K-m of 1.19 mm. This K-m value was comparable to its K-m values for MCTI or MCT2. MCT1 mRNA was found to be present markedly greater than that MCT2. Therefore, MCTI most probably acts on L-lactic acid uptake at RD cells. [C-14] L-Lactic acid efflux in RD cells was inhibited by alpha-cyano-4-hydroxycinnamate (CHC) but not by butyric acid, a substrate of MCT1. Accordingly, MCT2 or MCT4 is responsible for L-lactic acid efflux by RD cells. MCT4 mRNA was found to be present significantly greater than that MCT2. We conclude that MCTI is responsible for L-lactic acid uptake and L-lactic acid efflux is mediated by MCT4 in RD cells.

DOI PubMed CiNii

Uptake of irinotecan metabolite SN-38 by the human intestinal cell line Caco-2

T Itoh, S Itagaki, Y Sumi, T Hirano, Takemoto, I, K Iseki

CANCER CHEMOTHERAPY AND PHARMACOLOGY ( SPRINGER ) 55 ( 5 ) 420 - 424 2005.05 [Refereed]

Purpose: The aim of this study was to investigate the transport mechanisms of transporters that contribute to the intestinal uptake of 7-ethyl-10-hydroxycamptothecin (SN-38). Methods: Human intestinal epithelial Caco-2 cells were used to investigate the mechanistic basis of transepithelial uptake of SN-38. We investigated the characteristics of SN-38 uptake into Caco-2 cells. The effects of baicalin and sulfobromophthalein (BSP) on the uptake of SN-38 by Caco-2 cells were examined. Results: Uptake of SN-38 was significantly reduced at 4 degrees C. Baicalin inhibited the uptake of SN-38 in a concentration-dependent manner. BSP significantly reduced the uptake of SN-38. However, probenecid, pravastatin and grepafloxacin did not affect the uptake of SN-38. Conclusions: The results suggest that a specific transport system mediates the uptake of SN-38 across the apical membrane in Caco-2 cells.

DOI PubMed

Secretory transport of irinotecan metabolite SN-38 across isolated intestinal tissue

S Itagaki, Y Sumi, S Shimamoto, T Itoh, T Hirano, Takemoto, I, K Iseki

CANCER CHEMOTHERAPY AND PHARMACOLOGY ( SPRINGER ) 55 ( 5 ) 502 - 506 2005.05 [Refereed]

Purpose: The purpose of this study was to investigate the transport mechanisms of transporters that contribute to the intestinal efflux of 7-ethyl-10-hydroxycamptothecin (SN-38). Methods: The intestinal transport of SN-38 was studied in rat intestinal tissue mounted in Ussing chambers. Results: In the ileum, the level of transport from the serosal layer to the mucosal layer was significantly greater than that from the mucosal layer to the serosal layer, whereas a significant difference was not observed in the jejunum. This secretory transport required metabolic energy and was diminished by sulfobromophthalein. However, mitoxantrone, an inhibitor of breast cancer resistance protein (BCRP), did not affect the ileal secretion of SN-38. Conclusions: The results suggest that a specific transport system, which is distinct from BCRP, plays a major role in the secretion of SN-38 and that this secretory transport system predominantly exists in the ileum.

DOI PubMed

Food-drug interaction between ferulic acid and nateglinide involving the fluorescein/H+ cotransport system

S Itagaki, Y Kobayashi, Y Otsuka, S Kubo, M Kobayashi, T Hirano, K Iseki

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY ( AMER CHEMICAL SOC ) 53 ( 7 ) 2499 - 2502 2005.04 [Refereed]

In clinical, patients usually take many kinds of drugs at the same time. Thus, drug-drug interactions involving transporters can often directly affect the therapeutic safety and efficacy of many drugs. However, there have been few studies on food-drug interactions involving transporters. Dietary polyphenols have been widely assumed to be beneficial to human health. Polyphenols are commercially prepared and used as functional foods. We report here for the first time that ferulic acid, which is widely used as a functional food, affects the transport of clinical agents. It is important to be aware of the potential of food-drug interactions and to act in order to prevent undesirable and harmful clinical consequences.

DOI PubMed CiNii

Intestinal uptake of nateglinide by an intestinal fluorescein transporter

S Itagaki, Y Otsuka, S Kubo, H Okumura, Y Saito, M Kobayashi, T Hirano, K Seki

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES ( ELSEVIER SCIENCE BV ) 1668 ( 2 ) 190 - 194 2005.03 [Refereed]

Nateglinide, a novel oral hypoglycemic agent, rapidly reaches its maximum serum concentration after oral administration, suggesting that it is rapidly absorbed in the intestine. However, nateglinide itself is not transported by MCT1 or PEPT1. The aim of this study was to characterize the transporters on the apical side of the small intestine that are responsible for the rapid absorption of nateglinide. It has been reported that the uptake of fluorescein by Caco-2 cells occurs via an H+-driven transporter and that the intestinal fluorescein transporter is probably not MCTI. We examined the contribution of the fluorescein transporter to the uptake of nateglinide by Caco-2 cells. Fluorescein competitively inhibited H+-dependent nateglinide uptake. All of fluorescein transporter inhibitors examined reduced the uptake of nateglinide. Furthermore, nateglinide inhibited fluorescein uptake. We conclude that the intestinal nateglinide/H+ cotransport system is identical to the intestinal fluorescein/H+ cotransport system. (C) 2004 Elsevier B.V All rights reserved.

DOI

Intestinal uptake of nateglinide by an intestinal fluorescein transporter.

Itagaki S, Otsuka Y, Kubo S, Okumura H, Saito Y, Kobayashi M, Hirano T, Iseki K

Biochimica et biophysica acta ( 2 ) 1668 ( 2 ) 190 - 194 2005.03 [Refereed]

DOI

Intestinal uptake of nateglinide by an intestinal fluorescein transporter.

Itagaki S, Otsuka Y, Kubo S, Okumura H, Saito Y, Kobayashi M, Hirano T, Iseki K

Biochimica et biophysica acta 1668 ( 2 ) 190 - 194 2005.03 [Refereed] [International journal]

Nateglinide, a novel oral hypoglycemic agent, rapidly reaches its maximum serum concentration after oral administration, suggesting that it is rapidly absorbed in the intestine. However, nateglinide itself is not transported by MCT1 or PEPT1. The aim of this study was to characterize the transporters on the apical side of the small intestine that are responsible for the rapid absorption of nateglinide. It has been reported that the uptake of fluorescein by Caco-2 cells occurs via an H+-driven transporter and that the intestinal fluorescein transporter is probably not MCT1. We examined the contribution of the fluorescein transporter to the uptake of nateglinide by Caco-2 cells. Fluorescein competitively inhibited H+-dependent nateglinide uptake. All of fluorescein transporter inhibitors examined reduced the uptake of nateglinide. Furthermore, nateglinide inhibited fluorescein uptake. We conclude that the intestinal nateglinide/H+ cotransport system is identical to the intestinal fluorescein/H+ cotransport system.

DOI PubMed

H+-dependent transport mechanism of nateglinide in the brush-border membrane of the rat intestine

S Itagaki, Y Saito, S Kubo, Y Otsuka, Y Yamamoto, M Kobayashi, T Hirano, K Iseki

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS ( AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS ) 312 ( 1 ) 77 - 82 2005.01 [Refereed]

(-)-N-(trans-4-Isopropylcyclohexanecarbonyl)-D-phenylalanine (nateglinide) is a novel oral hypoglycemic agent possessing a carboxyl group and a peptide-type bond in its structure. Although nateglinide quickly reaches the maximal serum concentration after oral administration, nateglinide itself is not transported by PepT1 or MCT1. The aim of this study was to characterize the transporters on the apical side of the small intestine that are responsible for the rapid absorption of nateglinide. The uptake of nateglinide by rat intestinal brush-border membrane vesicles is associated with a proton-coupled transport system. Ceftibuten competitively inhibited H+-dependent nateglinide uptake. Glycylsarcosine (Gly-Sar), cephradine, and cephalexin did not significantly inhibit the uptake of nateglinide. The combination of Gly-Sar and nateglinide greatly reduced the uptake of ceftibuten. The effect of the combined treatment was significantly greater than that of Gly-Sar alone. Furthermore, nateglinide competitively inhibited H+-driven ceftibuten transporter-mediated ceftibuten uptake. Ceftibuten transport occurs via at least two H+-dependent transport systems: one is PepT1, and the other is the ceftibuten/H+ cotransport system. On the other hand, we demonstrated that nateglinide transport occurs via a single system that is H+ dependent but is distinct from PepT1 and may be identical to the ceftibuten/ H+ cotransport system.

DOI PubMed

Characterization of Secretory Intestinal Transport of Phenolsulfonphthalein

Shirou Itagaki, Makoto Chiba, Soji Shimamoto, Mitsuru Sugawara, Michiya Kobayashi, Katsumi Miyazaki, Takeshi Hirano, Ken Iseki

Drug Metabolism and Pharmacokinetics ( Japanese Society for the Study of Xenobiotics ) 20 ( 1 ) 72 - 78 2005 [Refereed]

DOI PubMed CiNii

Mechanism of L-lactic acid transport in L6 skeletal muscle cells.

Kobayashi M, Itagaki S, Hirano T, Iseki K

Drug metabolism and pharmacokinetics ( 5 ) 19 ( 5 ) 363 - 368 2004.10 [Refereed]

DOI PubMed CiNii

Pharmacokinetic modulation of irinotecan metabolites by sulphobromophthalein in rats

T Itoh, S Itagaki, K Sasaki, T Hirano, Takemoto, I, K Iseki

JOURNAL OF PHARMACY AND PHARMACOLOGY ( ROYAL PHARMACEUTICAL SOC GREAT BRITAIN ) 56 ( 6 ) 809 - 812 2004.06 [Refereed]

The purpose of this study was to modulate the pharmacokinetics of irinotecan metabolites, SN-38 and SN-38-glucuronide, by possibly reducing biliary excretion, which in turn could lower irinotecan toxicity. SN-38-glucuronide is associated with severe diarrhoea that occurs after irinotecan therapy as a result of enteric injury caused by SN-38. Sulphobromophthalein is used clinically as a drug for testing liver function and is considered to be a safe drug. We investigated the effect of sulphobro-mophthalein on the disposition of irinotecan metabolites after CPT-11 (7-ethyl-10-[10-4-(1-piperidino)-1-piperidino]-carbonyloxy-camptothecin) administration. Wistar rats were administered CPT-11 (500 mug/body) in saline as a bolus injection into the femoral vein through a catheter. The volume of drug solution injected into each animal was 1 mL. Rats were either administered CPT-11 alone or simultaneously with sulphobromophthalein (20 mg/body). After administration, blood and bile samples were taken at appropriate intervals and analysed by HPLC. Co-administration of sulphobromophthalein partially inhibited the biliary excretion of SN-38-glucuronide with a concomitant increase in its area under the plasma concentration-time curve (AUC) but did not significantly alter the biliary excretion and AUC of the active metabolite SN-38. These results suggested that cotreatment of CPT-11 with sulphobromophthalein might decrease intraluminal SN-38 concentrations without altering the pharmacokinetics of SN-38.

DOI PubMed

Comparison of urinary excretion of phenosulfonphthalein in an animal model for Wilson's disease (Long-Evans Cinnamon rats) with that in normal Wistar rats: Involvement of primary active organic anion transporter

Shirou Itagaki, Soji Shimamoto, Takeshi Hirano, Ken Iseki, Mitsuru Sugawara, Sachiho Nishimura, Michio Fujimoto, Michiya Kobayashi, Katsumi Miyazaki

Journal of Pharmacy and Pharmaceutical Sciences ( 2 ) 7 ( 2 ) 227 - 234 2004.05 [Refereed]

Purpose: The aim of this study was to determine the cause of the decline in phenolsulfonphthalein (PSP) excretion in Long-Evans Cinnamon (LEC) rats. Methods: The uptake of PSP into rat renal basolateral membrane vesicles (BLMV) was studied. Cyclosporin A (CYA) was used to modulate an ATP-dependent primary active transporter. PSP was intravenously injected into rats with or without CYA. The transcellular transport of PSP was examined by using primary cultured renal proximal tubule cells (PTC). Results: No significant difference was found between the uptake of PSP into renal BLMV of Wistar rats and that into renal BLMV of LEC rats. In the presence of CYA, the urinary excretion and the plasma concentrations of PSP in Wistar rats were decreased and increased, respectively. In primary cultured renal PTC from Wistar rats, the basal-to-apical transport of PSP was greater than that in the opposite direction and the basal-to-apical transport of PSP was substantially reduced by the addition of CYA. However, CYA did not affect the basal-to-apical transport of PSP in PTC from LEC rats. Conclusions: The results suggest that PSP is transported by primary active organic anion transporter and that the activity level of this transporter is reduced in LEC rats.

PubMed

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Papers - ITAGAKI Shiro