Serotonin 2A and 2B receptor-induced phrenic motor facilitation: differential requirement for spinal NADPH oxidase activity

Abstract Acute intermittent hypoxia (AIH) facilitates phrenic motor output by a mechanism that requires spinal serotonin (type 2) receptor activation, NADPH oxidase activity and formation of reactive oxygen species (ROS). Episodic spinal serotonin (5-HT) receptor activation alone, without changes in...

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Bibliographic Details
Published in:Neuroscience 2011-03, Vol.178, p.45-55
Main Authors: MacFarlane, P.M, Vinit, S, Mitchell, G.S
Format: Article
Language:English
Subjects:
Acetophenones - administration & dosage
Acetophenones - pharmacology
Action Potentials - drug effects
Action Potentials - physiology
Amphetamines - administration & dosage
Amphetamines - antagonists & inhibitors
Amphetamines - pharmacology
Animals
Biological and medical sciences
Fundamental and applied biological sciences. Psychology
Indoles - administration & dosage
Indoles - antagonists & inhibitors
Indoles - pharmacology
Injections, Spinal
Ketanserin - administration & dosage
Ketanserin - pharmacology
Male
NADPH oxidase
NADPH Oxidases - antagonists & inhibitors
NADPH Oxidases - physiology
Neurology
Onium Compounds - pharmacology
Phrenic Nerve - drug effects
Phrenic Nerve - enzymology
Phrenic Nerve - physiology
Pyridines - pharmacology
Rats
Rats, Sprague-Dawley
Receptor, Serotonin, 5-HT2A - physiology
Receptor, Serotonin, 5-HT2B - physiology
respiratory neuroplasticity
Serotonin 5-HT2 Receptor Agonists - administration & dosage
Serotonin 5-HT2 Receptor Agonists - pharmacology
Serotonin 5-HT2 Receptor Antagonists - administration & dosage
Serotonin 5-HT2 Receptor Antagonists - pharmacology
serotonin receptors
Thiophenes - administration & dosage
Thiophenes - antagonists & inhibitors
Thiophenes - pharmacology
Vertebrates: nervous system and sense organs
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Summary:Abstract Acute intermittent hypoxia (AIH) facilitates phrenic motor output by a mechanism that requires spinal serotonin (type 2) receptor activation, NADPH oxidase activity and formation of reactive oxygen species (ROS). Episodic spinal serotonin (5-HT) receptor activation alone, without changes in oxygenation, is sufficient to elicit NADPH oxidase-dependent phrenic motor facilitation (pMF). Here we investigated: (1) whether serotonin 2A and/or 2B (5-HT2A/B) receptors are expressed in identified phrenic motor neurons, and (2) which receptor subtype is capable of eliciting NADPH-oxidase-dependent pMF. In anesthetized, artificially ventilated adult rats, episodic C4 intrathecal injections (3×6 μl injections, 5 min intervals) of a 5-HT2A (DOI) or 5-HT2B (BW723C86) receptor agonist elicited progressive and sustained increases in integrated phrenic nerve burst amplitude (i.e. pMF), an effect lasting at least 90 min post-injection for both receptor subtypes. 5-HT2A and 5-HT2B receptor agonist-induced pMF were both blocked by selective antagonists (ketanserin and SB206553, respectively), but not by antagonists to the other receptor subtype. Single injections of either agonist failed to elicit pMF, demonstrating a need for episodic receptor activation. Phrenic motor neurons retrogradely labeled with cholera toxin B fragment expressed both 5-HT2A and 5-HT2B receptors. Pre-treatment with NADPH oxidase inhibitors (apocynin and diphenylenodium (DPI)) blocked 5-HT2B, but not 5-HT2A-induced pMF. Thus, multiple spinal type 2 serotonin receptors elicit pMF, but they act via distinct mechanisms that differ in their requirement for NADPH oxidase activity.
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2011.01.011