| Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2006: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
With the cells expressed cloned MOR-1, MOR-1A, MOR-1C or MOR-1E, the pharmacological character of these μ-opioid receptor splice variants were investigated. DAMGO, typical μ-opioid receptor agonist, showed high affinity and intrinsic activity in all of these splice variants. Moreover, amidino-TAPA, selective μ-opioid receptor agonist can lead the release of endogenous x-opioid peptides, also showed high intrinsic activity in all of these splice variants. These evidences clearly suggest that these 4 splice variants are not the μ-opioid receptor splice variants lead the release of endogenous κ-opioid peptides. To identify the splice varinats lead the release of endogenous κ-opioid peptides, we decide to identify first the amidino-TAPA-sensitive DAMGO-insensitive splice variants among more than 30 splice variants in behavioral experiment using the exon-specific antisense oligodeoxynucleotides for μ-opioid receptor gene. As the results, MOR-1J, MOR-1K and MOR-1L were identified as the amid
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ino-TAPA-sensitive DAMGO-insensitive splice variants. Moreover, additional experiments using the antisera against endogenous κ-opioid peptides, dynorphin A, dynorphin B or α-neoendorphin, identified that MOR-1J and MOR-1L are splice variants lead the release of dynorphin A, whereas MOR-1K is a splice variant lead the release of dynorphin B and α-neoendorphin. With above evidence, MOR-1J, MOR-1K and MOR-1L were cloned, but no intrinsic activity of amidino-TAPA was observed in the cells expressed cloned MOR-1K and MOR-1L. Since these 2 splice variants do not contain transmembrane structure, these splice variants may not have any function without other splice variants contain 7-transmembrane structure. To identify the pharmacological character of MOR-1J, MOR-1K and MOR-1L in its expressed cell, the functional characterization of heterodimer of these splice variants with other. Μ-opioid receptor splice variants, which contain 7-transmembrane structure, may be required. The cDNA of MOR-1J, MOR-1K and MOR-1L, cloned in the present project, are scheduled to be used in the new project accepted. Less
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