Serotonin 2A and 2B receptor-induced phrenic motor facilitation: differential requirement for spinal NADPH oxidase activity.
Serotonin 2A and 2B receptor-induced phrenic motor facilitation: differential requirement for spinal NADPH oxidase activity.
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DOI：
10.1016/j.neuroscience.2011.01.011
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发表时间：
2011-03-31
期刊：
影响因子：
3.3
通讯作者：
Mitchell GS
中科院分区：
文献类型：
--
作者：
MacFarlane PM;Vinit S;Mitchell GS
急性间歇性缺氧（AIH）通过脊髓5-羟色胺（2型）受体激活、NADPH氧化酶活性和活性氧（ROS）形成的机制促进膈运动输出。单独的脊髓5-羟色胺（5-HT）受体激活，而不改变氧合，足以引起NADPH氧化酶依赖性膈运动促进（pMF）。在这里，我们调查：1）5-羟色胺2A和/或2 B（5-HT 2a/B）受体是否在鉴定的膈运动神经元中表达，和2）哪种受体亚型能够引发NADPH氧化酶依赖性pMF。在麻醉、人工通气的成年大鼠中，间歇性C4鞘内注射（3 × 6µl注射，间隔5 min）5-HT 2a（DOI）或5-HT 2b（BW 723 C86）受体激动剂引起综合膈神经爆发振幅（即pMF）进行性和持续性增加，两种受体亚型的作用在注射后至少持续90 min。5-HT 2a和5-HT 2b受体激动剂诱导的pMF均被选择性拮抗剂（分别为酮色林和SB 206553）阻断，但不被另一种受体亚型的拮抗剂阻断。单次注射任一激动剂均未能引起pMF，表明需要间歇性受体激活。用霍乱毒素B片段逆行标记的膈运动神经元同时表达5-HT 2a和5-HT 2B受体。用NADPH氧化酶抑制剂（夹竹桃苷和DPI）预处理阻断5-HT 2b，但不阻断5-HT 2a诱导的pMF。因此，多种脊髓2型5-羟色胺受体引起pMF，但它们通过不同的机制起作用，不同的机制对NADPH氧化酶活性的要求不同。
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 × 6µl 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 minutes 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 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.
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影响因子：
3.3
作者：
Macfarlane, P. M.;Mitchell, G. S.
通讯作者：
Mitchell, G. S.
DOI：
10.1016/0034-5687(80)90113-9
发表时间：
1980-01-01
期刊：
RESPIRATION PHYSIOLOGY
影响因子：
--
作者：
MILLHORN, DE;ELDRIDGE, FL;WALDROP, TG
通讯作者：
WALDROP, TG
影响因子：
5.5
作者：
MacFarlane, P. M.;Satriotomo, I.;Mitchell, G. S.
通讯作者：
Mitchell, G. S.
影响因子：
5.3
作者：
Knapp, LT;Klann, E
通讯作者：
Klann, E
影响因子：
5.5
作者：
Baker, TL;Mitchell, GS
通讯作者：
Mitchell, GS