Evaluation of opioid and cannabinoid-induce respiratory center inhibition in medulla

阿片类药物和大麻素诱导延髓呼吸中枢抑制的评价

• 批准号: 14571469
• 负责人: TAKEDA Shinhiro
• 金额: $ 2.18万
• 依托单位: Nippon Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571469/
• 关键词: opioid; cannabinoid; membrane potential; respiratory center; Inspiratory neuron; Brainstem; Respiratory neuron

Membrane potential and resistance (Rm) were measured in inspiratory neurons in rostral ventrolateral medulla (RVLM) of the isolated brainstem-spinal cord preparation from newborn rats during bath application of opioids (μ-receptor agonists) and cannabinoid (CB1 receptor agonist : WIN 55212-2). μ-opioid receptor agonist caused reduction of final motor outputs by mainly inhibiting medullary inspiratory neuron network. This inhibition of inspiratory neurons seems to be due to both a pre-and postsynaptic inhibition. The central respiratory rhythm as reflected by the preinspiratory neuron burst rate was essentially unaltered by the agonists. WIN 55212-2 did not induced respiratory depression. Respiratory rate did not also change after application of CB1 receptor antagonist. Respiratory rate was decreased after application of μ-opioid receptor agonist from 8.4±1.9 to 2.7±1.8 bursts/min. This opioid-induced respiratory depression was parcially reversed by WIN 55212-2 from 2.7±1.8 to 6.32±1.9 bursts/min.

应用阿片类药物(μ受体激动剂)和大麻素(CB1受体激动剂：Win 55212-2)，测定新生大鼠分离的脑干-脊髓标本上延髓头端腹外侧吸气神经元的膜电位和膜电阻(Rm)。μ阿片受体激动剂主要通过抑制延髓吸气神经元网络而导致终末运动输出减少。这种对吸气神经元的抑制似乎是由于突触前和突触后的抑制。由吸气前神经元爆发率反映的中枢呼吸节律基本上不受激动剂的影响。Win 55212-2未引起呼吸抑制。应用CB1受体拮抗剂后，呼吸频率无明显变化。应用μ阿片受体激动剂后，呼吸频率从8.4±1.9次/分降至2.7±1.8次/分钟。WIN 55212-2可部分逆转阿片类药物引起的呼吸抑制，由2.7±1.8次/分钟降至6.32±1.9次/分钟。

项目成果

Akada S, Takeda S, Ogawa R: "Salicylate action on medullary inspiratory neuron activity on a brainstem-spinal cord preparation from newborn rats"Anesthesia & Analgesia. 96. 407-411 (2003)

Akada S、Takeda S、Okawa R：“水杨酸盐对新生大鼠脑干脊髓标本的髓质吸气神经元活动的作用”麻醉

Akada S, Takeda S, Ogawa R: "Salicylate action on medallary inspiratory neuron activity in a brainstem-spinal cord preparation from newborn rats"Anesthesia & Analgesia. 96・2. 407-411 (2003)

Akada S、Takeda S、Okawa R：“水杨酸盐对新生大鼠脑干脊髓制剂中奖章吸气神经元活动的作用”麻醉与镇痛 96・2（2003）。