Activation of the brain melanocortin system is required for leptin-induced modulation of chemorespiratory function.
Activation of the brain melanocortin system is required for leptin-induced modulation of chemorespiratory function.
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DOI：
10.1111/apha.12394
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发表时间：
2015-04
期刊：
影响因子：
--
通讯作者：
Colombari E
中科院分区：
文献类型：
--
作者：
Bassi M;Nakamura NB;Furuya WI;Colombari DS;Menani JV;do Carmo JM;da Silva AA;Hall JE;Colombari E
黑素皮质素受体（MC3/4R）介导瘦素的大部分代谢和心血管作用。在这里，我们测试了MC4R是否也有助于瘦素对呼吸功能的影响。对照测量后，雄性Holtzman大鼠每天微量注射瘦素、SHU9119 （MC3/4R拮抗剂）或SHU9119联合瘦素注入脑侧脑室，持续7天。治疗第6天，采用全身体积描记仪测定正常碳酸血症和高碳酸血症（7% CO2）时的潮气量（VT）、呼吸频率（fR）和肺通气量（VE）。同时测量基线平均动脉压（MAP）、心率（HR）和代谢率。在整个中枢神经系统瘦素受体缺失的小鼠（LepR/ netin -cre）或仅在propropiomanocortin神经元（LepR/POMC-cre）、MC4R敲除（MC4R−/−）和野生型小鼠中测量VE、VT和fR。与对照组相比，瘦素（5 μg/天）使小鼠体重（~17%）降低，通气反应增加，而SHU9119 （0.6 nmol/天）使小鼠体重（~18%）增加，通气反应降低（Lep: 2119±90 ml.min−1）。SHU9119: 997±67 ml.min−1。kg−1,vs PBS: 1379±91 ml.min−1 kg−1)。与PBS（106±3 mmHg）或单独使用SHU9119（109±3 mmHg）相比，瘦素治疗后MAP升高（130±2 mmHg）。SHU9119阻止瘦素对体重、MAP（102±3 mmHg）和高氧通气反应（1391±137 ml.min−1 kg−1）的影响。LepR/ netin -cre、LepR/POMC-cre和MC4R - / -小鼠对高氧血症的通气反应减弱。这些结果表明，中枢MC4R介导瘦素对高碳酸血症呼吸反应的影响。
Melanocortin receptors (MC3/4R) mediate most of the metabolic and cardiovascular actions of leptin. here we tested if MC4R also contributes to leptin’s effects on respiratory function. after control measurements, male Holtzman rats received daily microinjections of leptin, SHU9119 (MC3/4R antagonist) or SHU9119 combined with leptin infused into the brain lateral ventricle for 7 days. On the 6th day of treatment, tidal volume (VT), respiratory frequency (fR) and pulmonary ventilation (VE) were measured by whole-body plethysmography during normocapnia or hypercapnia (7% CO2). Baseline mean arterial pressure (MAP), heart rate (HR) and metabolic rate were also measured. VE, VT and fR were also measured in mice with leptin receptor deletion in the entire central nervous system (LepR/Nestin-cre) or only in proopiomelanocortin neurons (LepR/POMC-cre) and in MC4R knockout (MC4R−/−) and wild-type mice. leptin (5 μg/day) reduced body weight (~17%) and increased ventilatory response to hypercania, whereas SHU9119 (0.6 nmol/day) increased body weight (~18%) and reduced ventilatory responses compared to control-PBS group (Lep: 2119 ± 90 ml.min−1.kg−1and SHU9119: 997 ± 67 ml.min−1.kg−1, vs PBS: 1379 ± 91 ml.min−1.kg−1). MAP increased after leptin treatment (130 ± 2 mmHg) compared to PBS (106 ± 3 mmHg) or SHU9119 alone (109 ± 3 mmHg). SHU9119 prevented the effects of leptin on body weight, MAP (102 ± 3 mmHg) and ventilatory response to hypercania (1391 ±137 ml.min−1.kg−1). The ventilatory response to hypercania was attenuated in the LepR/Nestin-cre, LepR/POMC-cre and MC4R−/− mice. these results suggest that central MC4R mediate the effects of leptin on respiratory response to hypercapnia.
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影响因子：
3.3
作者：
Ciriello, J.;Moreau, J. M.
通讯作者：
Moreau, J. M.
DOI：
10.1152/ajpendo.00643.2012
发表时间：
2013-05-01
影响因子：
5.1
作者：
Laque, Amanda;Zhang, Yan;Muenzberg, Heike
通讯作者：
Muenzberg, Heike
影响因子：
8.3
作者：
Kuo, JJ;Silva, AA;Hall, JE
通讯作者：
Hall, JE
影响因子：
--
作者：
Inyushkina, E M;Merkulova, N A;Inyushkin, A N
通讯作者：
Inyushkin, A N
DOI：
10.1152/ajpregu.00503.2007
发表时间：
2007-10-01
影响因子：
2.8
作者：
McDowall, Lachlan M.;Horiuchi, Jouji;Dampney, Roger A. L.
通讯作者：
Dampney, Roger A. L.