期刊
NEUROSCIENCE
卷 178, 期 -, 页码 45-55出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuroscience.2011.01.011
关键词
serotonin receptors; NADPH oxidase; respiratory neuroplasticity
资金
- NIH [NIH HL-80209]
- Family Francis Foundation
- Craig H. Neilsen Foundation
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 (3x6 mu l 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. Published by Elsevier Ltd on behalf of IBRO.
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