Identification and Characterization of Novel Rat and Human Gonad-Specific Organic Anion Transporters

Suzuki, Takehiro; Onogawa, Tohru; Asano, Naoki; Mizutamari, Hiroya; Mikkaichi, Tsuyoshi; Tanemoto, Masayuki; Abe, Michiaki; Satoh, Fumitoshi; Unno, Michiaki; Nunoki, Kazuo; Suzuki, Masanori; Hishinuma, Takanori; Goto, Junichi; Shimosegawa, Tooru; Matsuno, Seiki; Ito, Sadayoshi; Abe, Takaaki

doi:10.1210/me.2002-0304

Cited by 86 publications

(53 citation statements)

References 51 publications

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“…This barrier function, the blood-testis barrier, mediates the absorption and excretion of essential nutrients and organic solutes and provides protection from toxic compounds (Russell, 1977). Recently, expression of several organic ion transporters such as multiple drug resistance proteins, multidrug resistance proteins, Oatps, OCTs, carnitine transporter 2 (CT2), and gonad-specific transporter 1 and 2 (GST-1/2) have been demonstrated in the testis (Enomoto et al, 2002;Suzuki et al, 2003;Augustine et al, 2005). The role of these transporters is to facilitate the supply of water-soluble compounds and to protect the reproductive system.…”

Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of Polyspecific Mouse Organic Solute Carrier Protein 1 (mOscp1)

Kobayashi

Tsuchiya²,

Hayashi³

et al. 2007

Drug Metab Dispos

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ABSTRACT:We succeeded in isolating the cDNA-encoding mouse organic solute carrier protein 1 (mOscp1) from a mouse testis cDNA library. mOscp1 consisted of 1137 base pairs that encoded a 379-amino acid protein, and the amino acid sequence was 85% identical to that of human OSCP1 (hOSCP1). Northern blot analysis revealed that the gene coding for mOscp1 is highly expressed in the testis, but not in other tissues. When expressed in Xenopus laevis oocytes, mOscp1 mediated the high-affinity transport of p-aminohippurate (PAH) (K m ‫؍‬ 18.8 ؎ 4.1 M) with Na ؉ independence.mOscp1 transported various kinds of structurally dissimilar drugs and chemicals such as probenecid, dehydroepiandrosterone sulfate, and glutarate with some differences in substrate specificity compared with hOSCP1. Cyclophosphamide inhibited the mOscp1-mediated PAH uptake. Immunohistochemical analysis revealed that the mOscp1 protein is localized in the plasma membrane side of Sertoli cells in the testis. Our results indicate that isolated mOscp1 is a polyspecific organic solute carrier protein and may be a key molecule for the testicular handling of organic solutes.

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Section: Discussionmentioning

confidence: 99%

Isolation and Characterization of Polyspecific Mouse Organic Solute Carrier Protein 1 (mOscp1)

Kobayashi

Tsuchiya²,

Hayashi³

et al. 2007

Drug Metab Dispos

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“…Several membrane transporter families have been identified, however only monocarboxylate transporter (MCT) 8, MCT 10 and organic anion-transporting polypeptides (OATPs) demonstrate a high degree of specificity towards thyroid hormone (22). The OATPs form a novel family of transporter proteins that have been detected in several tissues, including testis, in rodents and humans (22)(23)(24)(25)(26)(27)(28).…”

Section: Clinical Implications Of Altered Thyroid Functionmentioning

confidence: 99%

Clinical implications of altered thyroid status in male testicular function

Wajner

Wagner

Maia

2009

Arq Bras Endocrinol Metab

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Thyroid hormones are involved in the development and maintenance of virtually all tissues. Although for many years the testis was thought to be a thyroid-hormone unresponsive organ, studies of the last decades have demonstrated that thyroid dysfunction is associated not only with abnormalities in morphology and function of testes, but also with decreased fertility and alterations of sexual activity in men. Nowadays, the participation of triiodothyronine (T3) in the control of Sertoli and Leydig cell proliferation, testicular maturation, and steroidogenesis is widely accepted, as well as the presence of thyroid hormone transporters and receptors in testicular cells throughout the development process and in adulthood. But even with data suggesting that T3 may act directly on these cells to bring about its effects, there is still controversy regarding the impact of thyroid diseases on human spermatogenesis and fertility, which can be in part due to the lack of well-controlled clinical studies. The current review aims at presenting an updated picture of recent clinical data about the role of thyroid hormones in male gonadal function. RESUMOOs hormônios da tireoide estão envolvidos virtualmente no desenvolvimento e na manutenção de todos os tecidos. As gônadas masculinas foram, por décadas, consideradas insensíveis aos hormônios tireoidianos. No entanto, estudos mais recentes têm demonstrado que disfunções tireoidianas estão associadas não somente a anormalidades na morfologia e na função dos testículos, mas também à diminuição da fertilidade e alterações na atividade sexual masculina. Atualmente, o papel da triiodotironina (T3) no controle da proliferação das células de Sertoli e Leydig, maturação testicular e esteroidogênese é amplamente aceito, bem como a presença de transportadores e receptores para o hormônio tireoidiano nos testículos durante o período de desenvolvimento e a idade adulta. No entanto, apesar dos dados que indicam que o T3 atua diretamente nos testículos humanos, persistem controvérsias em relação ao impacto das doenças tireoidianas sobre a espermatogênese e a fertilidade, o que pode ser em parte devido à escassez de estudos clínicos nessa área. Essa revisão tem por objetivo apresentar um panorama de dados clínicos atualizados sobre o papel dos hormônios tireoidianos na função gonadal masculina. Arq Bras Endocrinol Metab. 2009;53(8):976-82 Descritores

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“…The overall amino acid sequence identities of human OATP4C1 with other human OATPs were 44.2% for human gonad-specific transporter (GST) (9) and 40.4% for OATP-E (22). Those of rat Oatp4c1 with other rat oatp family were 43.2% for rat oatp-E (22) and 36.4% for GST1 (9). The overall homology of human OATP4C1͞rat Oatp4c1 with other OATP family was below 35% (amino acid sequences were reviewed in refs.…”

Section: Isolation and Structural Analysis Of Human Oatp4c1 And Rat Omentioning

confidence: 99%

“…The OATP family is involved in the membrane transport of bile acids, conjugated steroids, thyroid hormone, eicosanoids, peptides, and numerous drugs including digoxin in many tissues (7)(8)(9). Rat oatp2 transports digoxin and is considered to be involved in the interaction of digoxin with drugs in the liver (10).…”

mentioning

confidence: 99%

Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney

Mikkaichi

Suzuki

Onogawa

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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251

239

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Digoxin, which is one of the most commonly prescribed drugs for the treatment of heart failure, is mainly eliminated from the circulation by the kidney. P-glycoprotein is well characterized as a digoxin pump at the apical membrane of the nephron. However, little is known about the transport mechanism at the basolateral membrane. We have isolated an organic anion transporter (OATP4C1) from human kidney. Human OATP4C1 is the first member of the organic anion transporting polypeptide (OATP) family expressed in human kidney. The isolated cDNA encodes a polypeptide of 724 aa with 12 transmembrane domains. The genomic organization consists of 13 exons located on chromosome 5q21. Its rat counterpart, Oatp4c1, is also isolated from rat kidney. Human OATP4C1 transports cardiac glycosides (digoxin, K m ‫؍‬ 7.8 M and ouabain, K m ‫؍‬ 0.38 M), thyroid hormone (triiodothyronine, Km ‫؍‬ 5.9 M and thyroxine), cAMP, and methotrexate in a sodiumindependent manner. Rat Oatp4c1 also transports digoxin (K m ‫؍‬ 8.0 M) and triiodothyronine (Km ‫؍‬ 1.9 M). Immunohistochemical analysis reveals that rat Oatp4c1 protein is localized at the basolateral membrane of the proximal tubule cell in the kidney. These data suggest that human OATP4C1͞rat Oatp4c1 might be a first step of the transport pathway of digoxin and various compounds into urine in the kidney.

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Identification and Characterization of Novel Rat and Human Gonad-Specific Organic Anion Transporters

Cited by 86 publications

References 51 publications

Isolation and Characterization of Polyspecific Mouse Organic Solute Carrier Protein 1 (mOscp1)

Isolation and Characterization of Polyspecific Mouse Organic Solute Carrier Protein 1 (mOscp1)

Clinical implications of altered thyroid status in male testicular function

Isolation and characterization of a digoxin transporter and its rat homologue expressed in the kidney

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