| Project/Area Number |
10671447
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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 | Nippon Medical School |
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Principal Investigator |
TAKEDA Shinhiro Nippon Medical School, Medicine, Assistant Professor, 医学部, 助手 (00247008)
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| Co-Investigator(Kenkyū-buntansha) |
IKEZAKI Hiroyuki Nippon Medical School, Medicine, Assistant Professor, 医学部, 助手 (20267131)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | opioids / medulla oblongata / respiratory center / hyperpolarization / membrane resistance |
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| Research Abstract |
Membrane potential and resistance (Rm) were measured in inspiratory (Insp, type I-III), preinspiratory (Pre-I) and expiratory (Exp) neurones in rostral ventrolateral medulla (RVLM) of the isolated brainstem-spinal cord preparation from newborn rats during bath application of μ-opioid receptor agonists morphine and DAGO (Try-D-Ala-Gly-[N MePhe]-Gly-ol), κ-opioid receptor agonist U50488 (trans-(±)-3, 4-Dichloro-N-methyl-N-[2-(1-pyrrolidiny)-cyclohexyl]-benzeneacetamide methanesulfonate) or δ-opioid receptor agonist DPDPE ({D-penィイD12,5ィエD1]-enkephalin).
DAGO (1 μM), morphine (10 μM) and U50488 (10 μM) led to a significant concomitant decrease in burst rate of C4 nerve activity and of Insp neurones. The opioid receptor agonists did not cause any significant effects in Pre-I and most Exp neurones. Forty percent of Insp neurones, which were inhibited with opioid receptor agonists, showed hyperpolarization and decreased Rm. Forth-five percent of Insp neurones also showed hyperpolarization and
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decreased Rm with opioid receptor agonists under tetrodotoxin perfusion.
A simultaneous intracellular recording from Insp neurones and an extracellular recording from Pre-I neurones confirmed the observation of excitatory postsynaptic potentials (EPSPs) or inhibitory postsynaptic potentials synchronized with the corresponding period of Pre-I neurones in Insp neurones during opioid-induced respiratory depression.
During opioid-induced respiratory depression, EPSPs evoked by stimulation to contralateral medulla oblongata became gentle in curve in Insp neurones. This suggests that opioid receptor agonists exert presynaptic action on Insp neurones. Even in hyperpolarized neurones, the EPSPs curve became gentle, which suggests the presence of neurones that simultaneously exhibit both pre- and postsynaptic inhibitory effects.
We conclude that opioid receptor agonists directly inhibit Insp neurones and disturb respiratory networks in the RVLM of newborn rats. The opioid-induced inhibitory action on Insp neurones is appeared to be both the pre- and postsynaptic sites. Less
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