Evaluation of opioid-induced respiratory center inhibition in medulla

阿片类药物引起的延髓呼吸中枢抑制的评价

• 批准号: 10671447
• 负责人: TAKEDA Shinhiro
• 金额: $ 1.73万
• 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: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671447/
• 关键词: opioids; medulla oblongata; respiratory center; hyperpolarization; membrane resistance

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 … More 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

在吸气时测量膜电位和电阻（Rm）。新生大鼠离体脑干-脊髓标本在μ阿片受体激动剂吗啡和DAGO作用下头端延髓腹外侧区（RVLM）吸气前（Pre-I）和呼气前（Exp）神经元的变化（Try-D-Ala-Gly-[N MePhe]-Gly-ol），κ-阿片受体激动剂U 50488（反式-（±）-3，4-二氯-N-甲基-N-[2-（1-吡咯烷基）-环己基]-苯乙酰胺甲磺酸盐）或δ-阿片受体激动剂DPDPE DAGO（1 μM）、吗啡（10 μM）和U 50488（10 μ M）导致C4神经活动和Insp神经元的爆发率显著降低。阿片受体激动剂在Pre-I和大多数Exp神经元中未引起任何显著影响。用阿片受体激动剂抑制的40%的Insp神经元表现出超极化和Rm降低。45%的Insp神经元也表现出超极化， ...更多信息 同时记录Insp神经元的细胞内电位和前I期神经元的细胞外电位，证实在阿片诱导的呼吸抑制过程中，Insp神经元的兴奋性突触后电位（EPSP）或抑制性突触后电位与前I期神经元的相应周期同步。刺激对侧延髓诱发的EPSPs在Insp神经元中曲线变得平缓。这表明阿片受体激动剂对Insp神经元发挥突触前作用。即使在超极化的神经元，EPSPs曲线变得温和，这表明存在的神经元，同时表现出前和突触后抑制effects.We得出结论，阿片受体激动剂直接抑制Insp神经元和干扰呼吸网络的新生大鼠RVLM。阿片类药物对Insp神经元的抑制作用表现在突触前和突触后两个部位。少