| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Physiology, Dartmouth Medical School, Lebanon, NH 03756-0001, USA2 Departments of Neurology and, Cellular & Molecular Physiology, Yale University, New Haven, CT, USA3 Advanced Targeting Systems, Inc, 11175-A Flintkote Ave, San Diego, CA, USA
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 (2x100 nl) (a) substance P–saporin (SP-SAP; 1µM) to kill NK1R-expressing neurones, (b) a novel conjugate of a monoclonal antibody to the serotonin transporter (SERT) and saporin (anti-SERT-SAP; 1µM) to kill serotonergic neurones, or (c) SP-SAP and anti-SERT-SAP together to kill both types. Controls received IgG-SAP injections (1µM). 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 CO2 in wakefulness and sleep by a similar amount. SP-SAP treatment decreased the averaged CO2 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.
(Received 5 December 2003;
accepted after revision 7 January 2004;
first published online 14 January 2004)
Corresponding author E. E. Nattie: Department of Physiology, Dartmouth Medical School, Borwell Bldg, Lebanon, NH 03756-0001, USA. Email: eugene.nattie{at}dartmouth.edu
This article has been cited by other articles:
|
|
 |
|
  A. C. Takakura, T. S. Moreira, R. L. Stornetta, G. H. West, J. M. Gwilt, and P. G. Guyenet Selective lesion of retrotrapezoid Phox2b-expressing neurons raises the apnoeic threshold in rats J. Physiol., June 15, 2008; 586(12): 2975 - 2991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Li and E. Nattie Serotonin transporter knockout mice have a reduced ventilatory response to hypercapnia (predominantly in males) but not to hypoxia J. Physiol., May 1, 2008; 586(9): 2321 - 2329. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Hodges, G. J. Tattersall, M. B. Harris, S. D. McEvoy, D. N. Richerson, E. S. Deneris, R. L. Johnson, Z.-F. Chen, and G. B. Richerson Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons J. Neurosci., March 5, 2008; 28(10): 2495 - 2505. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zanella, F. Watrin, S. Mebarek, F. Marly, M. Roussel, C. Gire, G. Diene, M. Tauber, F. Muscatelli, and G. Hilaire Necdin Plays a Role in the Serotonergic Modulation of the Mouse Respiratory Network: Implication for Prader-Willi Syndrome J. Neurosci., February 13, 2008; 28(7): 1745 - 1755. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Dias, T. B. Nucci, L. O. Margatho, J. Antunes-Rodrigues, L. H. Gargaglioni, and L. G. S. Branco Raphe magnus nucleus is involved in ventilatory but not hypothermic response to CO2 J Appl Physiol, November 1, 2007; 103(5): 1780 - 1788. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Nattie and A. Li Neurokinin-1 receptor-expressing neurons in the ventral medulla are essential for normal central and peripheral chemoreception in the conscious rat J Appl Physiol, December 1, 2006; 101(6): 1596 - 1606. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Li, S. Zhou, and E. Nattie Simultaneous inhibition of caudal medullary raphe and retrotrapezoid nucleus decreases breathing and the CO2 response in conscious rats J. Physiol., November 15, 2006; 577(1): 307 - 318. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Penatti, A. V. Berniker, B. Kereshi, C. Cafaro, M. L. Kelly, M. M. Niblock, H. G. Gao, H. C. Kinney, A. Li, and E. E. Nattie Ventilatory response to hypercapnia and hypoxia after extensive lesion of medullary serotonergic neurons in newborn conscious piglets J Appl Physiol, October 1, 2006; 101(4): 1177 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. F. Brandes, E. J. Zuperku, A. G. Stucke, D. Jakovcevic, F. A. Hopp, and E. A. E. Stuth Serotonergic Modulation of Inspiratory Hypoglossal Motoneurons in Decerebrate Dogs J Neurophysiol, June 1, 2006; 95(6): 3449 - 3459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sood, E. Raddatz, X. Liu, H. Liu, and R. L. Horner Inhibition of serotonergic medullary raphe obscurus neurons suppresses genioglossus and diaphragm activities in anesthetized but not conscious rats J Appl Physiol, June 1, 2006; 100(6): 1807 - 1821. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. T. Takakura, T. S. Moreira, E. Colombari, G. H. West, R. L. Stornetta, and P. G. Guyenet Peripheral chemoreceptor inputs to retrotrapezoid nucleus (RTN) CO2-sensitive neurons in rats J. Physiol., April 15, 2006; 572(2): 503 - 523. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Li and E. Nattie Catecholamine neurones in rats modulate sleep, breathing, central chemoreception and breathing variability J. Physiol., January 15, 2006; 570(2): 385 - 396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J Madden and S. F Morrison Hypoxic activation of arterial chemoreceptors inhibits sympathetic outflow to brown adipose tissue in rats J. Physiol., July 15, 2005; 566(2): 559 - 573. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C Taylor, A. Li, and E. E Nattie Medullary serotonergic neurones modulate the ventilatory response to hypercapnia, but not hypoxia in conscious rats J. Physiol., July 15, 2005; 566(2): 543 - 557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. B. Richerson Re: Retrotrapezoid nucleus: a litmus test for the identification of central chemoreceptors Exp Physiol, May 1, 2005; 90(3): 253 - 257. [Full Text] [PDF]
|
|
|
|
|
|
G. B. Richerson, W. Wang, M. R. Hodges, C. I. Dohle, and A. Diez-Sampedro Homing in on the specific phenotype(s) of central respiratory chemoreceptors Exp Physiol, May 1, 2005; 90(3): 259 - 266. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Hodges, C. Opansky, B. Qian, S. Davis, J. M. Bonis, K. Krause, L. G. Pan, and H. V. Forster Carotid body denervation alters ventilatory responses to ibotenic acid injections or focal acidosis in the medullary raphe J Appl Physiol, April 1, 2005; 98(4): 1234 - 1242. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Hodges, C. Opansky, B. Qian, S. Davis, J. Bonis, J. Bastasic, T. Leekley, L. G. Pan, and H. V. Forster Transient attenuation of CO2 sensitivity after neurotoxic lesions in the medullary raphe area of awake goats J Appl Physiol, December 1, 2004; 97(6): 2236 - 2247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. R. Hodges, P. Martino, S. Davis, C. Opansky, L. G. Pan, and H. V. Forster Effects on breathing of focal acidosis at multiple medullary raphe sites in awake goats J Appl Physiol, December 1, 2004; 97(6): 2303 - 2309. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. C. Taylor, A. Li, A. Green, H. C. Kinney, and E. E. Nattie Chronic fluoxetine microdialysis into the medullary raphe nuclei of the rat, but not systemic administration, increases the ventilatory response to CO2 J Appl Physiol, November 1, 2004; 97(5): 1763 - 1773. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
