| Budget Amount *help |
¥7,000,000 (Direct Cost: ¥7,000,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Research Abstract |
System L is one of the major routes to provide cells with neutral amino acids. Human L-type amino acid transporter 1 (hLAT1), a component of system L, is expressed in a wide variety of organs. Its highest expression levels are in the brain, placenta, testis, bone marrow and fetal liver, followed by peripheral leukocytes. lymph nodes and the thymus. In a previous study, LAT1 was found to act as a system L transporter at the blood-brain barrier and tumor tissue. On the other hand, hLAT2, an isoform of hLAT1, involves in the trans-cellular transport of neutral amino acids in epithelia blood-tissue barriers. Development of isoform-selective amino acid transporter agent is helpful about clarification of amino acid metabolic disease. We examined isoform-selectivity of 3-[^<125>I]iodo-α-methyl-L-tyrosine ([^<125>I]IMT), 4-[^<125>I]iodo-L-meta-tyrosine (4-[^<125>I]-mTyr) and 3-[-<125>I]iodo-L-tyrosine (3-[^<125>I]-Tyr) transport of the two human L-type amino acid transporters, hLAT1 and hLAT2 with human 4F2hc co-expressed Xenopus laevis oocytes. [^<125>I]IMT, 4-[^<125>I]-mTyr and 3-[^<125>I]-Tyr transport was hLAT1-selective. Cell line studies have revealed that systems L, A, T and B^<0,+> (and/or B^0) play a role in [^<125>I]IMT transport. Investigations on isoform-selectivity of transport of these compounds with other transporters are anticipated.
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