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5--HT_(2A)受体在尼可刹米增强新生大鼠延髓脑片呼吸放电中的作用

千智斌, 吴中海

南方医科大学生理学教研室.广东,广州 510515

摘要

该文探讨中枢呼吸兴奋剂尼可刹米对新生大鼠基本节律性呼吸产生和调节的影响及5--HT_(2A)受体在此过程中的作用。制作新生大鼠离体延髓脑片标本，包含面神经后核内侧区(the medial region of the nucleus retrofacialis, mNRF)并保留舌下神经根，给予灌流改良Kreb's液(modified Kreb's solution, MKS)，记录舌下神经根呼吸相关节律性放电活动(respiratory--related rhythmic discharge activity, RRDA)，观察不同浓度尼可刹米、5--HT_(2A)受体特异激动剂2,5--二甲氧基--4--碘苯基丙烷[1--(2,5--dimethoxy--4--iodophenyl)--2--aminopropane, DOI]、5--HT_(2A)受体特异拮抗剂酮舍林(ketanserine)以及联合使用尼可刹米和酮舍林对舌下神经根RRDA的影响。尼可刹米在0.5---7 #mu#g/mL范围内对延髓脑片RRDA有兴奋作用，在5 #mu#g/mL对吸气时程(inspiratory time, TI)、放电积分幅度(integral amplitude, IA)、呼吸周期(respiratory cycle, RC)等呼吸指标综合效果最显著。DOI明显延长TI、增强IA、缩短RC，对RRDA有兴奋作用。酮舍林明显缩短TI、减弱IA、延长RC，对RRDA有抑制作用。联合使用DOI和酮舍林对RRDA无明显作用。酮舍林可完全阻断尼可刹米对RC的作用，部分阻断尼可刹米对IA的作用，对尼可刹米引起的TI变化无明显影响。结果提示，尼可刹米增强新生大鼠离体延髓脑片舌下神经根RRDA，5--HT_(2A)受体可能是尼可刹米作用途径之一。

关键词： 面神经后核内侧区; 尼可刹米; 5-HT_(2A)受体; 延髓脑片

Role of 5--HT_(2A) receptor in increase in respiratory--related rhythmic discharge activity by nikethamide in neonatal rat transverse medullary slices

Qian Zhibin, Wu Zhonghai

Department of Physiology, Southern Medical University.Guangzhou 510515,Guangodng

Abstract

To investigate the effects of nikethamide on the generation and modulation of rhythmic respiration of neonatal rats and therole of 5-HT_(2A) receptor in this course, experiments were performed on the transverse medullary slices of neonatal rats (both sexes, 1-3 d) in vitro. The slices containing the medial region of the nucleus retrofacialis (mNRF) with the hypoglossal nerve rootlets were preparedin which the respiratory-related rhythmic discharge activity (RRDA) was recorded from the hypoglossal nerve rootlets by suctionelectrode. The possible role of nikethamide on RRDA was investigated by administration of an agonist of 5-HT_(2A) receptor, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), and an antagonist of 5-HT_(2A) receptor, ketanserine, dissolved in modified Kreb'ssolution (MKS). Thirty slices were randomly divided into five groups: Group 1: the slices were perfused with different concentrationsof nikethamide (0.5, 1, 3, 5, 7, 10 #mu#g/mL), and the most effective concentration was selected; Group 2: the slices were perfused with DOI(40 #mu#mol/L); Group 3: the slices were perfused with ketanserine (40 #mu#mol/L); Group 4: the slices were perfused with ketanserine + DOI;Group 5: the slices were perfused with nikethamide, then perfused with nikethamide + ketanserine after washout of nikethamide.Nikethamide increased RRDA in transverse medullary slices at 0.5-7 #mu#g/mL, and 5 #mu#g/mL was the most effective concentration. DOI increased RRDA with prolonged inspiratory time (TI), increased integral amplitude (IA), and shortened respiratory cycle (RC).Ketanserine decreased RRDA with shortened TI, decreased IA and prolonged RC. Ketanserine + DOI had no significant effects onRRDA. The effects of nikethamide on RC and IA were totally and partially reversed by additional application of ketanserine, but theeffect of nikethamide on TI was not influenced by ketanserine. It is proposed that nikethamide increases RRDA partly via 5-HT_(2A) receptors.

Key words: the medial region of nucleus retrofacialis;nikethamide;5-HT_(2A) receptor;transverse medullary slice

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引用本文：

千智斌, 吴中海. 5--HT_(2A)受体在尼可刹米增强新生大鼠延髓脑片呼吸放电中的作用[J]. 生理学报 2008; 60 (2): 216-220.

Qian Zhibin, Wu Zhonghai. Role of 5--HT_(2A) receptor in increase in respiratory--related rhythmic discharge activity by nikethamide in neonatal rat transverse medullary slices. Acta Physiol Sin 2008; 60 (2): 216-220 (in Chinese with English abstract).