| Project/Area Number |
12671516
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | University of Occupational and Environmental Health |
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Principal Investigator |
NANDATE Koichiroh (2001) UOEH, The faculty of medicine, instructor, 医学部, 助手 (50299632)
郡山 一明 (2000) 産業医科大学, 医学部, 講師 (80258623)
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| Co-Investigator(Kenkyū-buntansha) |
URYU Kayo UOEH, The faculty of medicine, instructor, 医学部, 助手 (20309975)
MINAMI Kouichiro UOEH, The faculty of medicine, assistant professor, 医学部, 講師 (70279347)
南立 宏一郎 産業医科大学, 医学部, 助手 (50299632)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Tramadol / Noradrenaline / Serotonin / Noradrenaline transpoter / G protein Coupled receptor / Muscarine receptor / tachykinin receptors / サブスタンス-P受容体 / 培養ウシ副腎髄質細胞 / カテコールアミン分泌 |
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| Research Abstract |
Tramadol is awidely used analgesic, but its mode of action is not well understood.
(1) To study the effects of tramadol on norepinephrine transporter (NET) function, we assayed the effect of tramadol on [3^]-norepinephrine ([3^]-NE) uptake and [ 3^]-desipramine binding to plasma membranes isolated from bovine adrenal medulla. Tramadol inhibited the desipramine-sensitive uptake of [ 3^]-NE by the cells in a concentration-dependent manner. Tramadol inhibited the specific binding of [ 3^]-desipramine to plasma membranes. These findings indicate that tramadol competitively inhibits norepinephrine transporter function at desipramine binding sites.
(2) Tramadol inhibited acetylchοDime-induced currents in oocytes expressing the m1 receptor. Although GF109203X, a protein kinase C inhibitor, increased the basal current, it had little effect on the inhibition of acetylcholine-induced currents by tramadol. In cultured bovine adrenal medullary cells, tramadol (100 nM-100 mM) suppressed muscarine-ind
… More
uced cyclic GMP accumulation. Moreover, tramadol inhibited the sped fie binding of [ 3^]quinuclydinyl benzylate ([ 3^]QNB). Scatchard analysis showed that tramadol increases the apparent dissociation constant (Kd) value without changing the maximal binding (Bmax), indicating competitive inhibition. These findings suggest that tramadol at clinically relevant concentrations Inhibits muscarinic receptor function via QNB-binding sites.
(3) We investigated the effect of tramadol on ion channel-mediated catecholamine secretion, nicotine-induced cytosolic Ca^<2+> concentration ([Ca<2+>]i) increases and membrane currents using Ca<2+>-imaging and whole-cell patch-clamp techniques in these cells. We also investigated the effects of tramadol on a7 nicotinic acetylcholine receptor ion channels expressed in Xenopus oocytes. Tramadol concentration-dependently inhibited carbachol-induced catecholamine secretion, whereas it had little effect on veratridine- or high K^+-induced catecholamine secretion. Tramadol suppressed nicotine-induced [Ca<2+>]i in a concentration-dependent manner. Less
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