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Serotonin 1A receptors stabilize respiratory activity through interneuronal disinhibition
Author(s) -
Manzke Till,
Guenther Ulf,
Schlaf Gerald,
Moerschel Michael,
Bidon Olivier,
Dutschmann Mathias,
Richter Diethelm
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a375-c
Subject(s) - 5 ht1a receptor , agonist , chemistry , serotonin , adenylyl cyclase , receptor , pharmacology , disinhibition , endocrinology , opioid , medicine , neuroscience , 5 ht receptor , biology
The serotonin receptor (5‐HTR) agonist 8‐OH‐DPAT recovers μ‐opioid receptor (μ‐OR)‐mediated respiratory depression. However, 8‐OH‐DPAT activates 5‐HT1A and 5‐HT7 receptor subtypes (5‐HT1AR, 5‐HT7R) that operate antagonistically on adenylyl cyclase (AC). According to previously published data (Manzke et al. 2003), activation of an antagonistic signaling cascade can recover μ‐OR‐evoked respiratory depression, while analgetic effects of opioids were maintained. 5‐HT1A and μ‐ORs operate on synergistic signaling pathways mediating suppression of AC, while 5‐HT7Rs are positively coupled to the AC through Gs‐proteins. Here we report that 5‐HT1A and 5‐HT7Rs are strongly co‐expressed in inhibitory glycine transporter 2 (GlyT2)‐positive neurons of the respiratory network including the Pre‐Boetzinger complex (PBC) and that their activation stimulate (5‐HT1AR) or depress (5‐HT7R) respiratory activity in the in situ perfused brainstem preparation. In vivo experiments confirmed that the beneficial effects of 8‐OH‐DPAT are exclusively mediated via 5‐HT1AR activation. We conclude that 8‐OH‐DPAT mediates the rescue phenomenon from opioid‐induced apnea without loss of analgesia through disinhibition of interneurons of the respiratory network. Funded by the CMPB Göttingen Lit.: Manzke, T et al., Science 301: 226‐229, 2003