Journal article
Medullary serotonergic neurones and adjacent neurones that express neurokinin-1 receptors are both involved in chemoreception in vivo
The Journal of physiology, Vol.556(Pt 1), pp.235-253
04/01/2004
DOI: 10.1113/jphysiol.2003.059766
PMCID: PMC1664900
PMID: 14724193
Abstract
Neurokinin-1 receptor (NK1R)-expressing neurones that are involved in chemoreception at the retrotrapezoid nucleus (Nattie & Li, 2002b) are also prominent at locations that contain medullary serotonergic neurones, which are chemosensitive in vitro. In medullary regions containing both types, we evaluated their role in central chemoreception by specific cell killing. We injected (2 x 100 nl) (a) substance P-saporin (SP-SAP; 1 microm) to kill NK1R-expressing neurones, (b) a novel conjugate of a monoclonal antibody to the serotonin transporter (SERT) and saporin (anti-SERT-SAP; 1 microm) to kill serotonergic neurones, or (c) SP-SAP and anti-SERT-SAP together to kill both types. Controls received IgG-SAP injections (1 microm). There was no double-labelling of NK1R-immunoreactive (ir) and tryptophan-hydroxylase (TPOH)-ir neurones. Cell (somatic profile) counts showed that NK1R-ir neurones in the SP-SAP group were reduced by 31%; TPOH-ir neurones in the anti-SERT-SAP group by 28%; and NK1R-ir and TPOH-ir neurones, respectively, in the combined lesion group by 55% and 31% (P < 0.001; two-way ANOVA; P < 0.05, Tukey's post hoc test). The treatments had no significant effect on sleep/wake time, body temperature, or oxygen consumption but all three reduced the ventilatory response to 7% inspired CO(2) in wakefulness and sleep by a similar amount. SP-SAP treatment decreased the averaged CO(2) responses (3, 7 and 14 days after lesions) in wakefulness and sleep by 21% and 16%, anti-SERT-SAP decreased the responses by 15% and 18%, and the combined treatment decreased the responses by 12% and 12% (P < 0.001; two-way ANOVA; P < 0.05, Tukey's post hoc test). We conclude that separate populations of serotonergic and adjacent NK1R-expressing neurones in the medulla are both involved in central chemoreception in vivo.
Details
- Title: Subtitle
- Medullary serotonergic neurones and adjacent neurones that express neurokinin-1 receptors are both involved in chemoreception in vivo
- Creators
- Eugene E Nattie - Department of Physiology, Dartmouth Medical School, Borwell Bldg, Lebanon, NH 03756-0001, USA. eugene.nattie@dartmouth.eduAihua LiGeorge B RichersonDouglas A Lappi
- Resource Type
- Journal article
- Publication Details
- The Journal of physiology, Vol.556(Pt 1), pp.235-253
- DOI
- 10.1113/jphysiol.2003.059766
- PMID
- 14724193
- PMCID
- PMC1664900
- NLM abbreviation
- J Physiol
- ISSN
- 0022-3751
- eISSN
- 1469-7793
- Publisher
- England
- Grant note
- R37 HL028066 / NHLBI NIH HHS HL 28066 / NHLBI NIH HHS R01 HL052539 / NHLBI NIH HHS MH 50063 / NIMH NIH HHS P01 HD036379 / NICHD NIH HHS HL 52539 / NHLBI NIH HHS R01 HL028066 / NHLBI NIH HHS P01-HD 36379 / NICHD NIH HHS
- Language
- English
- Date published
- 04/01/2004
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Neurosurgery
- Record Identifier
- 9984013205902771
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