the The Involvement of Respiration-Related Neurones in the Medullary Respiratory Rhythm Generation Center in the Opioid-Induced Respiratory Depression
| Project/Area Number |
13671557
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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 | HOKKAIDO UNIVERSITY |
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Principal Investigator |
TAKITA Koichi Hokkaido Univ., Grad. School of Med. Fac. Of Hokkaido Univ. Hospital, 医学部附属病院, 助手 (80261311)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Respirtory neurones / Whole cell recording / Blind patch clamp / New born rat / Immunohistochemistry / Opioid / Nociceptin / orphanin FQ / ブラインドパッチクランプ法 / Mu-オピオイド受容体 / ノシセプチン / 免疫組織染色 / C-Fos / 中枢性化学受容体 |
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| Research Abstract |
In brainstem-spinal cord preparations isolated from newborn rats, whole cell recording technique by blind patch clamp method was applied to record membrane potentials of respiration-related neurones in the medullary respiratory rhythm generating center. Neurones recorded was marked with 0.5% neurobiotin. To examine whether the neurones marked with neurbiotin have μ-opioid receptors, immunohistochemistry of μ-opioid receptors was also performed. In the present study, we have established the whole cell recording technique in brainstem-spinal cord preparations isolated from newborn rats, and the whole cell recordings from Type I, Type II, Type III inspiratory neurones and pre-inspiratory neurones in the medullary respiration center were successfully achieved. However, these respiratroy related-neurones did not show immunoreactivity of μ-opioid receptors.
To elucidate the roles nociceptin/orphanin FQ (N/OFQ) and the nociceptin/orphanin FQ peptide (NOP) receptor (previously termed ORL1 receptor) play in the medullary structures in the generation of respiratory rhythm, the respiratory effects of N/OFQ and the NOP antagonist, Comp B were examined, using in vitro newborn rat preparations. N/OFQ reduced fR in a concentration-dependent manner. Pretreatment with CompB 10μM prevented the N/OFQ 10 nM-induced fR reduction, whereas CompB itself did not affect fR. These results show that N/OFQ acts as a neuromodulator to reduce fR in the respiratory rhythm-generating center in the medulla oblongata, and this action of N/OFQ is mediated by NOP receptors.
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Report
(3 results)
Research Products
(2 results)
