Ⅱ组代谢性谷氨酸受体参与新生鼠离体延髓脑片呼吸节律性放电的调节

Group II metabotropic glutamate receptors is involved in the modulation of respiratory rhythmical discharge activity in neonatal rat medullary brain slices

目的探讨Ⅱ组代谢性谷氨酸受体在延髓离体脑片基本节律性呼吸放电调节中的作用。方法以改良Kreb＇s液恒温灌流新生Sprague-Dawley大鼠（03d）离体延髓脑片标本,稳定记录与之相连的舌下神经根的呼吸节律性放电活动（RRDA）后,第一组分别给予不同浓度Ⅱ组代谢性谷氨酸受体的特异性激动剂2R,4R-4-aminopyrrolidine-2,4-dicarboxylate（APDC）（10、20、50μmol/L）,观察各浓度舌下神经根RRDA的变化;第二组给予特异性拮抗剂（2S）-α-ethylglutamicacid（EGLU）（300μmol/L）,观察舌下神经根RRDA的变化;第三组先给予50μmol/LAPDC持续灌流10min后再给予50μmol/LAPDC＋300μmol/LEGLU灌流10min,观察各时间点舌下神经根RRDA的变化。结果单独给予APDC后,呼吸周期和呼气时程延长、吸气时程缩短、吸气放电积分幅度降低,且有浓度依赖性;单独给予EGLU后,呼吸周期及呼气时程缩短,对吸气时程和放电积分幅度没有影响,且APDC的作用可以被EGLU部分逆转。结论Ⅱ组代谢性谷氨酸受体参与了哺乳动物基本呼吸节律的调节。

Objective To explore the role of group II metabotropic glutamate receptors in the modulation of basic respiratory rhythm. Methods Neonatal （0-3 days） SD rats of either sex were used. The medulla oblongata brain slice containing the medial region of the nucleus retrofacialis （mNRF） and the hypoglossal nerve rootlets was prepared, and the surgical procedure was performed in the modified Kreb＇s solution （MKS） with continuous carbogen （95% O2 and 5% CO2） within 3 min. The brain slices were quickly transferred to a recording chamber and continuously perfused with oxygen-saturated MKS at a rate of 4-6 ml/min at 27-29 ℃. Eighteen medulla oblongata slices were divided into 3 groups and treated for 10 min with group II metabotropic glutamate receptor-specific agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate （APDC） （at concentrations of 10, 20, 50 μmol/L）, group II metabotropic glutamate receptor antagonist （2S）-α-ethylglutamic acid （EGLU） （300 μmol/L）, or APDC （50 μmol/L）＋EGLU （300 μmol/L） after a 10 min APDC （50 μmol/L） application. Respiratory rhythmical discharge activity （RRDA） of the rootlets of the hypoglossal nerve was recorded by suction electrodes. Results APDC produced a dose-dependent inhibitory effect on the RRDA, prolonging the respiratory cycle and expiratory time and decreasing the integral amplitude and inspiratory time. EGLU induced a significant decrease in the respiratory cycle and expiratory time. The effect of APDC on the respiratory rhythm was partially reversed by the application of APDC＋EGLU. Conclusion Group II metabotropic glutamate receptors are probably involved in the modulation of the RRDA in isolated neonatal rat brainstem slice.