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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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Citing This Article:

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).