Related Content
Search Google Scholar for:
More Information
Related Jobs from ScienceCareers
|
|
Science 11 July 2003: Vol. 301. no. 5630, pp. 226 - 229 DOI: 10.1126/science.1084674
|
|
Reports
5-HT4(a) Receptors Avert Opioid-Induced Breathing Depression Without Loss of Analgesia
Till Manzke,1*
Ulf Guenther,2*
Evgeni G. Ponimaskin,1
Miriam Haller,1
Mathias Dutschmann,1
Stephan Schwarzacher,3
Diethelm W. Richter1
Opiates are widely used analgesics in anesthesiology, but they have serious adverse effects such as depression of breathing. This is caused by direct inhibition of rhythm-generating respiratory neurons in the Pre-Boetzinger complex (PBC) of the brainstem. We report that serotonin 4(a) [5-HT 4(a)] receptors are strongly expressed in respiratory PBCneurons and that their selective activation protects spontaneous respiratory activity. Treatment of rats with a 5-HT 4 receptorspecific agonist overcame fentanyl-induced respiratory depression and reestablished stable respiratory rhythm without loss of fentanyl's analgesic effect. These findings imply the prospect of a fine-tuned recovery from opioid-induced respiratory depression, through adjustment of intracellular adenosine 3',5'-monophosphate levels through the convergent signaling pathways in neurons.
1 Department of Neuro- and Sensory Physiology, University of Goettingen, Humboldtallee 23, 37073 Goettingen, Germany. 2 Center of Anesthesiology, University of Goettingen, Robert-KochStreet 40, 37075 Goettingen, Germany. 3 Department of Anatomy, Kreuzbergring 36, 37075 Goettingen, Germany.
* These authors contributed equally to this work.
To whom correspondence should be addressed. E-mail: d.richter{at}gwdg.de
Read the Full Text
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
- Activation of the retrotrapezoid nucleus by posterior hypothalamic stimulation.
- M. G. Fortuna, R. L. Stornetta, G. H. West, and P. G. Guyenet (2009)
J. Physiol.
587, 5121-5138
| Abstract »
| Full Text »
| PDF »
- Serotonin targets inhibitory synapses to induce modulation of network functions.
- T. Manzke, M. Dutschmann, G. Schlaf, M. Morschel, U. R. Koch, E. Ponimaskin, O. Bidon, P. M. Lalley, and D. W. Richter (2009)
Phil Trans R Soc B
364, 2589-2602
| Abstract »
| Full Text »
| PDF »
- The potency of different serotonergic agonists in counteracting opioid evoked cardiorespiratory disturbances.
- M. Dutschmann, H. Waki, T. Manzke, A. E. Simms, A. E. Pickering, D. W. Richter, and J. F. R. Paton (2009)
Phil Trans R Soc B
364, 2611-2623
| Abstract »
| Full Text »
| PDF »
- Opioid receptor mechanisms at the hypoglossal motor pool and effects on tongue muscle activity in vivo.
- M. Hajiha, M.-A. DuBord, H. Liu, and R. L. Horner (2009)
J. Physiol.
587, 2677-2692
| Abstract »
| Full Text »
| PDF »
- The Counteraction of Opioid-Induced Ventilatory Depression by the Serotonin 1A-Agonist 8-OH-DPAT Does Not Antagonize Antinociception in Rats In Situ and In Vivo.
- U. Guenther, T. Manzke, H. Wrigge, M. Dutschmann, J. Zinserling, C. Putensen, and A. Hoeft (2009)
Anesth. Analg.
108, 1169-1176
| Abstract »
| Full Text »
| PDF »
- Raphe Neurons Stimulate Respiratory Circuit Activity by Multiple Mechanisms via Endogenously Released Serotonin and Substance P.
- K. Ptak, T. Yamanishi, J. Aungst, L. S. Milescu, R. Zhang, G. B. Richerson, and J. C. Smith (2009)
J. Neurosci.
29, 3720-3737
| Abstract »
| Full Text »
| PDF »
- Inhibitory and excitatory effects of {micro}-, {delta}-, and {kappa}-opioid receptor activation on breathing in awake turtles, Trachemys scripta.
- S. M. Johnson, M. E. Kinney, and L. M. Wiegel (2008)
Am J Physiol Regulatory Integrative Comp Physiol
295, R1599-R1612
| Abstract »
| Full Text »
| PDF »
- The 2008 Carl Ludwig Lecture: retrotrapezoid nucleus, CO2 homeostasis, and breathing automaticity.
- P. G. Guyenet (2008)
J Appl Physiol
105, 404-416
| Abstract »
| Full Text »
| PDF »
- The Effects of Fentanyl-Like Opioids and Hydromorphone on Human 5-HT3A Receptors.
- M. Wittmann, T. Schaaf, I. Peters, S. Wirz, B. W. Urban, and M. Barann (2008)
Anesth. Analg.
107, 107-112
| Abstract »
| Full Text »
| PDF »
- Opioids and the control of respiration.
- K. T. S. Pattinson (2008)
Br. J. Anaesth.
100, 747-758
| Abstract »
| Full Text »
| PDF »
- Metabotropic glutamate receptors activate dendritic calcium waves and TRPM channels which drive rhythmic respiratory patterns in mice.
- S. L. Mironov (2008)
J. Physiol.
586, 2277-2291
| Abstract »
| Full Text »
| PDF »
- Anatomical and functional development of the pre-Botzinger complex in prenatal rodents.
- M. Thoby-Brisson and J. J. Greer (2008)
J Appl Physiol
104, 1213-1219
| Abstract »
| Full Text »
| PDF »
- Generation of Eupnea and Sighs by a Spatiochemically Organized Inspiratory Network.
- A. Ruangkittisakul, S. W. Schwarzacher, L. Secchia, Y. Ma, N. Bobocea, B. Y. Poon, G. D. Funk, and K. Ballanyi (2008)
J. Neurosci.
28, 2447-2458
| Abstract »
| Full Text »
| PDF »
- Defects in Breathing and Thermoregulation in Mice with Near-Complete Absence of Central Serotonin Neurons.
- 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 (2008)
J. Neurosci.
28, 2495-2505
| Abstract »
| Full Text »
| PDF »
- Necdin Plays a Role in the Serotonergic Modulation of the Mouse Respiratory Network: Implication for Prader-Willi Syndrome.
- S. Zanella, F. Watrin, S. Mebarek, F. Marly, M. Roussel, C. Gire, G. Diene, M. Tauber, F. Muscatelli, and G. Hilaire (2008)
J. Neurosci.
28, 1745-1755
| Abstract »
| Full Text »
| PDF »
- Serotonergic Neurons Activate Chemosensitive Retrotrapezoid Nucleus Neurons by a pH-Independent Mechanism.
- D. K. Mulkey, D. L. Rosin, G. West, A. C. Takakura, T. S. Moreira, D. A. Bayliss, and P. G. Guyenet (2007)
J. Neurosci.
27, 14128-14138
| Abstract »
| Full Text »
| PDF »
- 5-Hydroxytryptamine 1A/7 and 4{alpha} Receptors Differentially Prevent Opioid-Induced Inhibition of Brain Stem Cardiorespiratory Function.
- X. Wang, O. Dergacheva, H. Kamendi, C. Gorini, and D. Mendelowitz (2007)
Hypertension
50, 368-376
| Abstract »
| Full Text »
| PDF »
- Effects of medullary Raphe stimulation on fictive lung ventilation during development in Rana catesbeiana.
- O. Belzile, R. Gulemetova, and R. Kinkead (2007)
J. Exp. Biol.
210, 2046-2056
| Abstract »
| Full Text »
| PDF »
- Neurokinin Receptor-Expressing Pre-Botzinger Complex Neurons in Neonatal Mice Studied In Vitro.
- J. A. Hayes and C. A. Del Negro (2007)
J Neurophysiol
97, 4215-4224
| Abstract »
| Full Text »
| PDF »
- Ampakines Alleviate Respiratory Depression in Rats.
- J. Ren, B. Y. Poon, Y. Tang, G. D. Funk, and J. J. Greer (2006)
Am. J. Respir. Crit. Care Med.
174, 1384-1391
| Abstract »
| Full Text »
| PDF »
- High Sensitivity to Neuromodulator-Activated Signaling Pathways at Physiological [K+] of Confocally Imaged Respiratory Center Neurons in On-Line-Calibrated Newborn Rat Brainstem Slices..
- A. Ruangkittisakul, S. W. Schwarzacher, L. Secchia, B. Y. Poon, Y. Ma, G. D. Funk, and K. Ballanyi (2006)
J. Neurosci.
26, 11870-11880
| Abstract »
| Full Text »
| PDF »
- Point:Counterpoint: The parafacial respiratory group (pFRG)/pre-Botzinger complex (preBotC) is the primary site of respiratory rhythm generation in the mammal.
- H. Onimaru, I. Homma, J. L. Feldman, and W. A. Janczewski (2006)
J Appl Physiol
100, 2094-2098
| Full Text »
| PDF »
- Opiate slowing of feline respiratory rhythm and effects on putative medullary phase-regulating neurons.
- P. M. Lalley (2006)
Am J Physiol Regulatory Integrative Comp Physiol
290, R1387-R1396
| Abstract »
| Full Text »
| PDF »
- Zacopride and 8-OH-DPAT reverse opioid-induced respiratory depression and hypoxia but not catatonic immobilization in goats.
- L. C. R. Meyer, A. Fuller, and D. Mitchell (2006)
Am J Physiol Regulatory Integrative Comp Physiol
290, R405-R413
| Abstract »
| Full Text »
| PDF »
- Distinct rhythm generators for inspiration and expiration in the juvenile rat.
- W. A. Janczewski and J. L. Feldman (2006)
J. Physiol.
570, 407-420
| Abstract »
| Full Text »
| PDF »
- Agonist-Directed Trafficking of Response by Endocannabinoids Acting at CB2 Receptors.
- J. L. Shoemaker, M. B. Ruckle, P. R. Mayeux, and P. L. Prather (2005)
J. Pharmacol. Exp. Ther.
315, 828-838
| Abstract »
| Full Text »
| PDF »
- Morphine Side Effects in {beta}-Arrestin 2 Knockout Mice.
- K. M. Raehal, J. K. L. Walker, and L. M. Bohn (2005)
J. Pharmacol. Exp. Ther.
314, 1195-1201
| Abstract »
| Full Text »
| PDF »
- Uncoupling and Endocytosis of 5-Hydroxytryptamine 4 Receptors: DISTINCT MOLECULAR EVENTS WITH DIFFERENT GRK2 REQUIREMENTS.
- G. Barthet, F. Gaven, B. Framery, K. Shinjo, T. Nakamura, S. Claeysen, J. Bockaert, and A. Dumuis (2005)
J. Biol. Chem.
280, 27924-27934
| Abstract »
| Full Text »
| PDF »
- D1-dopamine receptor agonists prevent and reverse opiate depression of breathing but not antinociception in the cat.
- P. M. Lalley (2005)
Am J Physiol Regulatory Integrative Comp Physiol
289, R45-R51
| Abstract »
| Full Text »
| PDF »
- Emergence of the Pre-Botzinger Respiratory Rhythm Generator in the Mouse Embryo.
- M. Thoby-Brisson, J.-B. Trinh, J. Champagnat, and G. Fortin (2005)
J. Neurosci.
25, 4307-4318
| Abstract »
| Full Text »
| PDF »
- Fluorescent Tagging of Rhythmically Active Respiratory Neurons within the Pre-Botzinger Complex of Rat Medullary Slice Preparations.
- S. Pagliardini, T. Adachi, J. Ren, G. D. Funk, and J. J. Greer (2005)
J. Neurosci.
25, 2591-2596
| Abstract »
| Full Text »
| PDF »
- Transient attenuation of CO2 sensitivity after neurotoxic lesions in the medullary raphe area of awake goats.
- M. R. Hodges, C. Opansky, B. Qian, S. Davis, J. Bonis, J. Bastasic, T. Leekley, L. G. Pan, and H. V. Forster (2004)
J Appl Physiol
97, 2236-2247
| Abstract »
| Full Text »
| PDF »
- Opioid-induced Respiratory Depression: Are 5-HT4a Receptor Agonists the Cure?.
- H. Eilers and M. A. Schumacher (2004)
Mol. Interv.
4, 197-199
| Abstract »
| Full Text »
| PDF »
- Attenuated Response to Stress and Novelty and Hypersensitivity to Seizures in 5-HT4 Receptor Knock-Out Mice.
- V. Compan, M. Zhou, R. Grailhe, R. A. Gazzara, R. Martin, J. Gingrich, A. Dumuis, D. Brunner, J. Bockaert, and R. Hen (2004)
J. Neurosci.
24, 412-419
| Abstract »
| Full Text »
| PDF »
- On the opiate trail of respiratory depression.
- D. R. McCrimmon and G. F. Alheid (2003)
Am J Physiol Regulatory Integrative Comp Physiol
285, R1274-R1275
| Full Text »
| PDF »
- Separating Opioid Analgesia from Opioid Asphyxia.
- (2003)
Journal Watch (General)
2003, 3
| Full Text »
|
|