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[PMID]: | 14734677 |
[Au] Autor: | Shikano N; Kanai Y; Kawai K; Ishikawa N; Endou H |
[Ad] Endereço: | Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki, Japan. sikano@ipu.ac.jp |
[Ti] Título: | Transport of 99mTc-MAG3 via rat renal organic anion transporter 1. |
[So] Source: | J Nucl Med;45(1):80-5, 2004 Jan. | [Is] ISSN: | 0161-5505 |
[Cp] País de publicação: | United States |
[La] Idioma: | eng |
[Ab] Resumo: | UNLABELLED: Recently, complementary DNA (cDNA) encoding a p-aminohippurate (PAH) transporter designated rat organic anion transporter 1 (OAT1) was isolated. OAT1, a multispecific organic anion transporter at the basolateral membrane, is exclusively expressed in the middle segment of the proximal tubule in the rat kidney. It has been proposed that OAT1 is indirectly involved in PAH uptake via the Na(+) dicarboxylate cotransporter. In this study, in molecular biologic experiments using OAT1-expressing Xenopus laevis oocytes, we obtained evidence that (99m)Tc-mercaptoacetylglycylglycylglycine (MAG3) is transported via OAT1. METHODS: Capped OAT1 complementary RNA (cRNA) was synthesized from library plasmid cDNA linearized with BamHI using in vitro transcription. Defolliculated oocytes were injected with 10 ng of OAT1 cRNA. Two to 3 d after injection, uptake of (99m)Tc-MAG3 was measured using ND96 solution containing 18.5 kBq of (99m)Tc-MAG3. Before the uptake experiments, OAT1-expressing oocytes were preincubated for 2 h with 1 mmol/L glutarate (a dicarboxylate), to generate an outwardly directed glutarate gradient. Then, after incubation for 60 min at room temperature, radioactivity of oocytes was determined. For the inhibition experiments, uptake was assessed in the absence or presence of inhibitor: 2 mmol/L of PAH, o-iodohippurate (OIH), probenecid, 3,5-diiodo-4-pyridone-N-acetate (iodopyracet), furosemide, ethacrynic acid, glucoheptonate, maleic acid, L-Tyr, or tetraethylammonium (TEA) or 0.1 mmol/L of 2,4-dinitrophenol (DNP). RESULTS: Na(+) had a significant effect on (99m)Tc-MAG3 uptake (P < 0.05). Accumulated glutarate stimulated simultaneous (99m)Tc-MAG3 uptake and glutarate excretion (P < 0.001). The following compounds significantly inhibited (99m)Tc-MAG3 uptake: PAH, 8.5% +/- 16.2% of (99m)Tc-MAG3 uptake in the absence of an inhibitor; OIH, 26.4% +/- 21.7%; probenecid, 29.1% +/- 12.4%; iodopyracet, 15.8% +/- 7.9%; furosemide, 30.5% +/- 15.7%; ethacrynic acid, 21.6% +/- 10.6%; glucoheptonate, 35.6% +/- 22.6%; and maleic acid, 60.1% +/- 18.7%. (99m)Tc-MAG3 accumulation in Xenopus laevis oocytes was not significantly inhibited by TEA, L-Tyr, or DNP. CONCLUSION: The following substances had a cis-inhibitory effect on (99m)Tc-MAG3 transport: PAH, OIH, probenecid, iodopyracet, furosemide, ethacrynic acid, and glucoheptonate. Glutarate had a trans-stimulative effect on (99m)Tc-MAG3 transport. (99m)Tc-MAG3 acts as a substrate of OAT1, an organic anion/dicarboxylate exchanger. |
[Mh] Termos MeSH primário: |
Oócitos/metabolismo Canais de Potássio/metabolismo Sódio/metabolismo Tecnécio Tc 99m Mertiatida/farmacocinética
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[Mh] Termos MeSH secundário: |
Animais Transporte Biológico Ativo/efeitos dos fármacos Transporte Biológico Ativo/fisiologia Células Cultivadas Furosemida/farmacologia Iodoperaceto/farmacologia Taxa de Depuração Metabólica Oócitos/diagnóstico por imagem Oócitos/efeitos dos fármacos Canais de Potássio/efeitos dos fármacos Probenecid/farmacologia Técnica de Diluição de Radioisótopos Cintilografia Ratos Proteínas Recombinantes/metabolismo Sódio/farmacologia Xenopus laevis
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[Pt] Tipo de publicação: | COMPARATIVE STUDY; JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (Potassium Channels); 0 (Recombinant Proteins); 36ITO9SKQJ (Technetium Tc 99m Mertiatide); 7LXU5N7ZO5 (Furosemide); 9NEZ333N27 (Sodium); PO572Z7917 (Probenecid); ZTK4026YJ5 (Iodopyracet) |
[Em] Mês de entrada: | 0404 |
[Cu] Atualização por classe: | 161124 |
[Lr] Data última revisão:
| 161124 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 040122 |
[St] Status: | MEDLINE |
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