Die von Serotoninrezeptor 1A modulierte Dephosphorylierung des Glyzinrezeptors α3 Ein neuer molekularer Mechanismus der Atmungskontrolle zur Kompensation opioidinduzierter Atemdepression ohne Verlust der Analgesie [Serotonin receptor 1A-modulated dephosphorylation of glycine receptor α3: A new molecular mechanism of breathing control for compensation of opioid-induced respiratory depression without loss of analgesia]

T Manzke; M Niebert; U R Koch; A Caley; S Vogelgesang; A M Bischoff; S Hülsmann; E Ponimaskin; U Müller; T G Smart; Robert J Harvey; D W Richter

doi:10.1007/s00482-011-1044-1

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Die von Serotoninrezeptor 1A modulierte Dephosphorylierung des Glyzinrezeptors α3 Ein neuer molekularer Mechanismus der Atmungskontrolle zur Kompensation opioidinduzierter Atemdepression ohne Verlust der Analgesie [Serotonin receptor 1A-modulated dephosphorylation of glycine receptor α3: A new molecular mechanism of breathing control for compensation of opioid-induced respiratory depression without loss of analgesia]

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Die von Serotoninrezeptor 1A modulierte Dephosphorylierung des Glyzinrezeptors α3 Ein neuer molekularer Mechanismus der Atmungskontrolle zur Kompensation opioidinduzierter Atemdepression ohne Verlust der Analgesie [Serotonin receptor 1A-modulated dephosphorylation of glycine receptor α3: A new molecular mechanism of breathing control for compensation of opioid-induced respiratory depression without loss of analgesia]

T Manzke, M Niebert, U R Koch, A Caley, S Vogelgesang, A M Bischoff, S Hülsmann, E Ponimaskin, U Müller, T G Smart, …

Der Schmerz, Vol.25(3), pp.272-281

2011

DOI: https://doi.org/10.1007/s00482-011-1044-1

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Abstract

respiratory depression

phosphorylation

serotinin 1A receptor

adenylate cyclase

opioids

To control the breathing rhythm the medullary respiratory network generates periodic salvo activities for inspiration, post-inspiration and expiration. These are under permanent modulatory control by serotonergic neurons of the raphe which governs the degree of phosphorylation of the inhibitory glycine receptor α3. The specific activation of serotonin receptor type 1A (5-HTR 1A), which is strongly expressed in the respiratory neurons, functions via inhibition of adenylate cyclase and the resulting reduction of the intracellular cAMP level and a gradual dephosphorylation of the glycine receptor type α3 (GlyRα3). This 5-HTR 1A-GlyRα3 signal pathway is independent of the μ-opioidergic transduction pathway and via a synaptic inhibition caused by an increase in GlyRα3 stimulates a disinhibition of some target neurons not only from excitatory but also from inhibitory neurons. Our physiological investigations show that this 5-HTR 1A-GlyRα3 modulation allows treatment of respiratory depression due to opioids without affecting the desired analgesic effects of opioids. The molecular mechanism presented here opens new pharmacological possibilities to treat opioid-induced respiratory depression and respiratory disorders due to disturbed inhibitory synaptic transmission, such as hyperekplexia.

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Title: Die von Serotoninrezeptor 1A modulierte Dephosphorylierung des Glyzinrezeptors α3 Ein neuer molekularer Mechanismus der Atmungskontrolle zur Kompensation opioidinduzierter Atemdepression ohne Verlust der Analgesie [Serotonin receptor 1A-modulated dephosphorylation of glycine receptor α3: A new molecular mechanism of breathing control for compensation of opioid-induced respiratory depression without loss of analgesia]
Authors: T Manzke (Author) - Universität Göttingen, Germany
M Niebert (Author) - Universität Göttingen, Germany
U R Koch (Author) - Universität Göttingen, Germany
A Caley (Author) - School of Pharmacy, United Kingdom
S Vogelgesang (Author) - DFG Forschungszentrum für Molekulare Physiologie des Gehirns (CMPB), Germany
A M Bischoff (Author) - Universität Göttingen, Germany
S Hülsmann (Author) - Universität Göttingen, Germany
E Ponimaskin (Author) - Universität Göttingen, Germany
U Müller (Author) - Universität Heidelberg, Germany
T G Smart (Author) - University College, United Kingdom
Robert J Harvey (Author) - School of Pharmacy, United Kingdom
D W Richter (Author) - Universität Göttingen, Germany
Publication details: Der Schmerz, Vol.25(3), pp.272-281
Publisher: Springer
Date published: 2011
DOI: 10.1007/s00482-011-1044-1
ISSN: 0932-433X
Organisation Unit: School of Health; University of the Sunshine Coast, Queensland; School of Health and Sport Sciences - Legacy; Centre for Bioinnovation; School of Health and Behavioural Sciences - Legacy
Language: English; German
Record Identifier: 99451165802621
Output Type: Journal article

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